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BIOMARKER:

AR positive

i
Other names: AR, AIS, DHTR, HUMARA, NR3C4, SBMA, SMAX1, Androgen receptor
Entrez ID:
Related biomarkers:
3d
Aberrant androgen action in prostatic progenitor cells induces oncogenesis and tumor development through IGF1 and Wnt axes. (PubMed, Nat Commun)
Correlations between altered androgen, IGF1, and Wnt/β-catenin signaling are also identified in human prostate cancer samples, uncovering a dynamic regulatory loop initiated by the AR through prostate cancer development. Co-inhibition of androgen and Wnt-signaling pathways significantly represses the growth of AR-positive tumor cells in both ex-vivo and in-vivo, implicating co-targeting therapeutic strategies for these pathways to treat advanced prostate cancer.
Journal
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IGF1 (Insulin-like growth factor 1)
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AR positive • IGF1 elevation
3d
Dynamic plasticity of prostate cancer intermediate cells during androgen receptor-targeted therapy. (PubMed, Cell Rep)
In the presence of castration or AR inhibitors, intermediate cells were necessary and sufficient for therapy-induced conversion of human PC cells to an NSE-high transcriptional status. Using hormone add-back studies, treatment-induced PSA-NSE transcriptional plasticity was reversible in PTEN-deficient PC cells but not in the presence of secondary genetic driver genes, including MYCN.
Journal
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PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
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AR positive
15d
Clinical • P2 data
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AR (Androgen receptor)
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AR positive • AR negative
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capecitabine • Nubeqa (darolutamide)
16d
Phase II Study of Enzalutamide for Patients With Androgen Receptor-Positive Salivary Gland Cancers (Alliance A091404). (PubMed, J Clin Oncol)
Enzalutamide demonstrated limited activity in AR+ SGC, failing to meet protocol-defined success in part because of a lack of response durability. Strategies to enhance the efficacy of antiandrogen therapy are needed.
P2 data • Journal
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HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
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AR positive • AR expression
|
enzalutamide capsule
27d
MicroRNA-99b-5p targets mTOR/AR axis, induces autophagy and inhibits prostate cancer cell proliferation. (PubMed, Tumour Biol)
Our data suggest that miR-99b functions as a tumor suppressor by targeting the mTOR/AR axis in PCa cells, implicating miR-99b as a novel biomarker and therapeutic target for PCa management.
Journal
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MIR99B (MicroRNA 99b)
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AR positive • AR negative
|
docetaxel • enzalutamide capsule • sirolimus
27d
Morphological Features and Immunohistochemical Profiling of Male Breast Gynaecomastia; A Large Tissue Microarray Study. (PubMed, Front Oncol)
The identification of a low Ki67 proliferative index and the mixed cytokeratin profile in gynaecomastia differentiates this benign condition from male breast cancer. Therefore, Ki67 and cytokeratins can help in the differential diagnosis from histological mimics in the routine diagnostic work up.
Journal
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ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
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AR positive • AR expression
27d
The Clinicopathological Significance and Prognostic Value of Androgen Receptor in Endometrial Carcinoma: A Meta-Analysis. (PubMed, Front Oncol)
AR expression is significantly associated favorable characteristics including low-grade disease, early-stage disease, negative lymph node status, and lack of the lymphovascular invasion and a specific histology-endometrioid cancer. However, AR is not an independent prognostic factor.
Retrospective data • Review • Journal
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AR (Androgen receptor)
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AR positive • AR expression
29d
The Potential Tumor-Suppressor DHRS7 Inversely Correlates with EGFR Expression in Prostate Cancer Cells and Tumor Samples. (PubMed, Cancers (Basel))
Importantly, analysis of patient samples revealed a negative correlation between DHRS7 and EGFR expression, both at the mRNA and protein levels, and DHRS7 expression correlated positively with patient survival rates. These results suggest a protective role for DHRS7 in PCa.
Journal
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EGFR (Epidermal growth factor receptor) • AR (Androgen receptor)
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EGFR expression • AR positive • AR expression • AR negative
1m
Aspalathus linearis suppresses cell survival and proliferation of enzalutamide-resistant prostate cancer cells via inhibition of c-Myc and stability of androgen receptor. (PubMed, PLoS One)
Our results suggested that GRT treatment suppressed the cell proliferation and survival of enzalutamide-resistant PCa cells via inhibition of c-Myc, induction of apoptosis, as well as the suppression of expression, signaling and stability of AR. GRT is a potential adjuvant therapeutic agent for enzalutamide-resistant PCa.
Journal • IO biomarker
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MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • AR (Androgen receptor) • CDK1 (Cyclin-dependent kinase 1) • KLK3 (Kallikrein-related peptidase 3)
|
AR positive • MYC overexpression • MYC expression • AR expression
|
enzalutamide capsule
1m
Ceritinib is a novel triple negative breast cancer therapeutic agent. (PubMed, Mol Cancer)
To improve the response of AR antagonist in AR positive TNBC, we designed a novel combinational strategy comprised of enzalutamide and ceritinib to treat AR TNBC tumors through the dual blockade of androgen-dependent and androgen-independent AR signaling pathways. Furthermore, we introduced a novel therapeutic combination of ceritinib and paclitaxel for AR negative or AR-low TNBCs and this combination inhibited tumor growth to a great extent. All agents used in our study are FDA-approved, and thus the proposed combination therapy will likely be useful in the clinic.
Journal
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ER (Estrogen receptor)
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AR positive • AR negative
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Xalkori (crizotinib) • paclitaxel • Zykadia (ceritinib) • enzalutamide capsule
1m
TNBC Profiling Based on Protein Expression of Biomarkers (EACR 2022)
AR expression was seen in patients with late disease onset and smaller tumours but was associated with poor survival and lower sTILs scores. The observed trend will be validated with a more extensive data set and associated with response to treatment.
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
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HER-2 expression • AR positive • EGFR positive • AR expression • AR negative
1m
Long-term prognostic factors for a high-risk oral squamous cell carcinoma population (EACR 2022)
No statistically relevant correlations were seen in the case of ER and PR. Conclusion Her-2 is a valuable marker for predicting long-term prognosis and Her-2 positive OSCC patients may benefit from anti-Her-2 targeted therapy.
Clinical
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AR (Androgen receptor)
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HER-2 positive • HER-2 negative • HER-2 expression • AR positive • AR expression
2ms
HDL-mediated reduction of cholesterol content inhibits the proliferation of prostate cancer cells induced by LDL: Role of ABCA1 and proteasome inhibition. (PubMed, Biofactors)
Bortezomib, a proteasome inhibitor, restored ABCA1 expression and HDL ability to promote cholesterol removal from PC3; consequently, HDL inhibited the proliferation of PC3 cells induced by LDL only after bortezomib pre-treatment. In conclusion, the antiproliferative activity of HDL on AR-positive and AR-null PCa cells also rely on cholesterol removal, a process in which the ABCA1 transporter plays a key role.
Journal
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AR (Androgen receptor) • ABCA1 (ATP Binding Cassette Subfamily A Member 1)
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AR positive
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bortezomib
2ms
Pembrolizumab and Enobosarm in Treating Patients With Androgen Receptor Positive Metastatic Triple Negative Breast Cancer (clinicaltrials.gov)
P2, N=18, Active, not recruiting, City of Hope Medical Center | N=29 --> 18 | Trial completion date: Nov 2021 --> Jan 2023
Enrollment change • Trial completion date
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HER-2 negative • AR positive • PGR expression • ER expression
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Keytruda (pembrolizumab) • Ostarine (enobosarm)
2ms
Androgen and oestrogen receptor co-expression determines the efficacy of hormone receptor-mediated radiosensitisation in breast cancer. (PubMed, Br J Cancer)
While radiosensitising in AR + TNBC, AR inhibition does not modulate radiation sensitivity in AR+/ER+ breast cancer. The efficacy of ER antagonists in combination with RT may also be dependent on AR expression.
Journal
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ER (Estrogen receptor) • AR (Androgen receptor)
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ER positive • HR positive • AR positive • AR expression • ER expression
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tamoxifen • enzalutamide capsule • fulvestrant • Erleada (apalutamide) • Nubeqa (darolutamide) • seviteronel (INO-464)
3ms
TiP. Randomized, Multicenter, Phase 3 Study to Evaluate the Combination of Enobosarm and Abemaciclib Compared With Estrogen-Blocking Agent for the Second-Line Treatment of AR+, ER+, HER2– Metastatic Breast Cancer in Patients Who Have Previously Received Palbociclib and an Estrogen-Blocking Agent Combination Therapy (MBCC 2022)
If first-line therapy for mBC was a nonsteroidal aromatase inhibitor (AI) plus palbociclib (Ibrance), then the patient is randomized to either enobosarm plus abemaciclib (Verzenio) or fulvestrant. Secondary end points include objective response rate, duration of response, overall survival, change from baseline in Short Physical Performance Battery (SPPB), change in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ), and change in body composition as measured by dual-energy x-ray absorptiometry (DEXA). Status The study is currently ongoing, and it is anticipated that enrollment will be completed this year.
Clinical • P3 data • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
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ER positive • HER-2 negative • AR positive • AR negative
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Ibrance (palbociclib) • Verzenio (abemaciclib) • fulvestrant • Ostarine (enobosarm)
3ms
TiP. Randomized, Multicenter, International Phase 3 ARTEST Study to Evaluate the Efficacy and Safety of Enobosarm Versus Active Control for the Treatment of AR+, ER+, HER2– Metastatic Breast Cancer in Patients Who Previously Received an Estrogen-Blocking Agent and CDK4/6 Inhibitor (MBCC 2022)
Approximately 210 subjects with AR+, ER+, HER2– mBC and with AR nuclei staining of 40% or greater are being randomized 1:1 to either enobosarm 9-mg oral daily dose or an active comparator (either exemestane, everolimus [Afinitor], or a selective estrogen receptor modulator; physician’s choice). The secondary objectives/end points of this study include the objective response rate, duration of response, overall survival, change from baseline in Short Physical Performance Battery (SPPB), and change in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ). Status The study is currently ongoing, and it is anticipated that enrollment will be completed this year
Clinical • P3 data
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
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ER positive • HER-2 negative • AR positive • AR expression
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everolimus • exemestane • Ostarine (enobosarm)
3ms
Hormone receptors AR, ER, PR and growth factor receptor Her-2 expression in oral squamous cell carcinoma: Correlation with overall survival, disease-free survival and 10-year survival in a high-risk population. (PubMed, PLoS One)
No statistically relevant correlations were seen in the case of ER and PR. In conclusion, Her-2 may be a valuable marker for predicting long-term prognosis of OSCC patients.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
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HER-2 positive • HER-2 negative • HER-2 expression • AR positive • AR expression
3ms
A chemical probe for BAG1 targets androgen receptor-positive prostate cancer through oxidative stress signaling pathway. (PubMed, iScience)
Furthermore, A4B17 outperformed the clinically approved antagonist enzalutamide in inhibiting cell proliferation and prostate tumor development in a mouse xenograft model. BAG1 inhibitors therefore offer unique opportunities for antagonizing AR action and prostate cancer growth.
Journal
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BAG1 (BAG Cochaperone 1) • HSPA4 (Heat Shock Protein Family A (Hsp70) Member 4)
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AR positive
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enzalutamide capsule
3ms
Brest cancer in a patient with non classical Congenital Adrenal Hyperplasia- Link or Coincidence? (ISGE 2022)
We also performed a long Dexamethasone suppression test (2x2mg), with optimal inhibition of cortisol (0.25microg/dl), and also Androgens (17-OH-Progesteron 0.55ng/ml, Testosterone 0.25ng/ml, Androstendione 0.61ng/ml) and Progesterone (0.46ng/ml), thus excluding a tumoral cause of hyperandrogenism... Hormonal dependent breast cancer in patients with Congenital Adrenal Hyperplasia may represent a treatment challenge, and suppression of adrenal Progesterone and Androgens may be necessary in addition to antiestrogenic treatment. Also a link between longstanding, nontreated CAH and androgen receptor positive breast cancer may be suspected and further studies are needed in this direction.
Clinical
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HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • AR (Androgen receptor)
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HER-2 negative • AR positive
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dexamethasone
3ms
Phase 3 ENABLAR-2 study to evaluate enobosarm and abemaciclib combination compared to estrogen-blocking agent for the second-line treatment of AR+, ER+, HER2- metastatic breast cancer in patients who previously received palbociclib and estrogen-blocking agent combination therapy. (ASCO 2022)
The planned sample size is 186 patients randomized 1:1 to enobosarm + abemaciclib OR fulvestrant if the first line of therapy for MBC was a non-steroidal AI plus palbociclib, until disease progression, toxicity, or loss of clinical benefit. The key objectives are to determine the safety and efficacy of enobosarm and abemaciclib combination versus an alternative estrogen blocking agent with the primary endpoint of PFS. Secondary endpoints include ORR, duration of response, overall survival, change from baseline in Short Physical Performance Battery (SPPB), change in EORTC Quality of Life Questionnaire (EORTC-QLQ) and change in body composition as measured by DEXA.
Clinical • P3 data • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
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HER-2 negative • AR positive
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Ibrance (palbociclib) • Verzenio (abemaciclib) • fulvestrant • Ostarine (enobosarm)
3ms
Translational relevance of HER2-low expression in triple-negative breast cancer: A retrospective single-center study. (ASCO 2022)
The non-significant trend towards a lower survival for Her2-low TNBCs, coupled with a surprisingly lower histologic grade and a higher AR positivity needs to be further evaluated in larger studies. Further translational research to optimize treatment for this subgroup is needed.
Retrospective data • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
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HR positive • HER-2 overexpression • HER-2 amplification • HER-2 negative • HER-2 expression • AR positive • HER-2 underexpression
3ms
Chemical degrader enhances the treatment of androgen receptor-positive triple-negative breast cancer. (PubMed, Arch Biochem Biophys)
By evaluating the therapeutic efficacies in vitro and in vivo, we validated that AR-PROTAC was superior to enzalutamide, an AR inhibitor. Specifically, AR-PROTAC at 100 nM reduced BT549 cell viability by up to ∼80%, and AR-PRTOAC at 10 mg/kg suppressed tumor growth by ∼60% when administrated intratumorally in subcutaneous BT549 tumor mice model. Overall, these results demonstrate for the first time that PROTAC holds promise to enhance the treatment of AR-positive TNBC.
Journal
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AR (Androgen receptor)
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AR positive
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enzalutamide capsule
4ms
Small extracellular vesicle-mediated ITGB6 siRNA delivery downregulates the αVβ6 integrin and inhibits adhesion and migration of recipient prostate cancer cells. (PubMed, Cancer Biol Ther)
Furthermore, treatment with sEVs encapsulating ITGB6 siRNA significantly reduces cell adhesion and migration of PrCa cells on an αVβ6-specific substrate, LAP-TGFβ1. Our results demonstrate an approach for specific targeting of the αVβ6 integrin in PrCa cells using sEVs encapsulating ITGB6-specific siRNAs.
Journal
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AR (Androgen receptor) • TGFB1 (Transforming Growth Factor Beta 1)
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AR positive • AR expression • AR negative • AR wild-type
4ms
Proteomic and Transcriptomic Profiling Reveals Mitochondrial Oxidative Phosphorylation as Therapeutic Vulnerability in Androgen Receptor Pathway Active Prostate Tumors. (PubMed, Cancers (Basel))
Of these, we functionally confirmed the role of mitochondrial metabolism in AR-positive CRPC cell lines. Our data highlight how the integration of transcriptomic and proteomic approaches and PDX systems as preclinical models can potentially map the connectivity of poorly understood signaling pathways in metastatic prostate cancer.
Journal
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AR (Androgen receptor)
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AR positive
4ms
Menin Enhances Androgen Receptor-Independent Proliferation and Migration of Prostate Cancer Cells. (PubMed, Mol Cells)
Furthermore, wound-healing assay results showed that menin promoted cell migration in AR-independent cellular contexts. Overall, these findings suggest a critical function of menin in tumorigenesis and provide a rationale for drug development against menin toward targeting high-risk metastatic PCa, especially those independent of AR.
Journal
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AR (Androgen receptor)
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AR positive
4ms
Systemic therapy for salivary gland malignancy: current status and future perspectives. (PubMed, Jpn J Clin Oncol)
Future directions might include a more comprehensive genomic screening approach (usually next-generation sequencing-based) and combination strategies using immune checkpoint inhibitors. These are rare malignancies that require ongoing effort in the conduct of high-quality clinical trials.
Journal • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • AR (Androgen receptor) • NTRK (Neurotrophic receptor tyrosine kinase)
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HER-2 positive • AR positive • NTRK positive • NTRK fusion
4ms
Castration-resistant prostate cancer patient presenting with whole genome doubling with CDK-12 mutation. (PubMed, BMC Med Genomics)
This report is the first case of a Japanese patient presenting with WGD, who survived more than 13 years with multimodal chemotherapies and radiotherapies.
Journal
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CDK12 (Cyclin dependent kinase 12)
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AR positive • CDK12 mutation
4ms
GLI3 and androgen receptor are mutually dependent for their malignancy-promoting activity in ovarian and breast cancer cells. (PubMed, Cell Signal)
Our findings suggest that GLI3 and AR not only physically interact, but also are mutually dependent for their malignancy-promoting activity in ovarian and breast cancer cells. GLI3-specific inhibitors may be novel therapeutics for AR-expressing ovarian and breast cancers.
Journal
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AR (Androgen receptor) • GLI3 (GLI Family Zinc Finger 3)
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AR positive • AR expression • GLI3 expression
4ms
Androgen Receptor as an Emerging Feasible Biomarker for Breast Cancer. (PubMed, Biomolecules)
Targeting AR alone or other therapeutic agents provides alternatives to existing therapy for breast cancer. Therefore, AR expression will be necessary if AR-targeted treatment is to be used.
Review • Journal
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AR (Androgen receptor)
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AR positive • AR expression
5ms
Trial completion date • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
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AR positive
|
paclitaxel • enzalutamide capsule
5ms
Quadruple negative breast tumors in African American women express factors associated with worse prognosis compared to triple negative tumors (AACR 2022)
In our study of AAs, a statistically significant association was noted between QNBC tumors and poorer prognosis. The high prevalence of AR negativity of TNBCs in AAs could explain observed worse outcomes and supports the existence of a unique subtype of Bca known as QNBC, worthy of scientific attention.
Clinical
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor) • VIM (Vimentin) • ENG (Endoglin)
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HER-2 expression • AR positive • VIM expression
5ms
Exploring the role of CRM1 in DNA repair pathway in prostate cancer cells (AACR 2022)
Treatment of PCa cells with Selinexor affected expression, localization, and kinetics of DNA repair leading to unrepaired DNA and induced apoptosis.
BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • AR (Androgen receptor) • CCND1 (Cyclin D1) • RAD51 (RAD51 Homolog A) • BRCA (Breast cancer early onset) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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AR positive
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Xpovio (selinexor)
5ms
PT-112 induces potent mitochondrial stress and immunogenic cell death in human prostate cancer cell lines (AACR 2022)
PT-112 was broadly active in the PC cell lines tested, while sparing benign prostate cells, indicative of PT-112 cancer cell selectivity and of activity that crosses the varied malignant prostate phenotypes, including androgen receptor positive and negative cell lines. Cell death was primarily apoptotic, as shown by the inhibitory effects of Z-VAD-fmk. Consistent with prior work reported in glycolytic murine cells, in this PC cell panel PT-112 induced mtROS accumulation and mitochondrial membrane depolarization, as well as DAMP release, demonstrating that these may be fundamental and linked responses of cancer cells to PT-112.
Preclinical
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AR (Androgen receptor) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • CALR (Calreticulin) • RIPK1 (Receptor Interacting Serine/Threonine Kinase 1)
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AR positive • HIF1A expression
|
imifoplatin (PT-112)
5ms
Trop-2 expression in triple-negative breast cancer according to histological subtype: correlations with tumor infiltrating lymphocytes (TILs) and survival (AACR 2022)
Given the approval of sacituzumab govitecan in unselected TNBC, its evaluation in other breast cancer settings and the emergence of other Trop-2 targeted antibody-drug conjugates, Trop-2 emerges as an important drug target in solid tumors. Trop-2-expression of patients with TNBC diagnosed between 2000-2017 at UZ Leuven was determined with IHC (ab227689, Abcam) (continuous and categorical variables, high 201-300, medium 100-200 and low <100 H-score)... In patients with TNBC in a large tertiary center, higher Trop-2 expression was correlated with apocrine histology, higher AR expression, more associated DCIS, more LVI and nodal involvement. There was no correlation between Trop-2 expression and sTILs or outcome.
Tumor-Infiltrating Lymphocyte • BRCA Biomarker
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AR (Androgen receptor) • BRCA (Breast cancer early onset)
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AR positive • AR expression
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Trodelvy (sacituzumab govitecan-hziy)
5ms
Modeling Breast Cancer in Organoid and Intraductal Models. (PubMed, Methods Mol Biol)
We present protocols to create estrogen receptor positive (ER+) and androgen receptor positive (AR+) breast cancer models by combining organoid culture with mammary intraductal injection.
Journal
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ER (Estrogen receptor) • AR (Androgen receptor)
|
ER positive • AR positive
6ms
Androgen Deprivation Therapy (ADT) and Pembrolizumab for Advanced Stage Androgen Receptor-positive Salivary Gland Carcinoma (clinicaltrials.gov)
P2, N=20, Recruiting, Manish Patel | Trial completion date: Jan 2023 --> Jan 2024 | Trial primary completion date: Jan 2022 --> Jan 2023
Trial completion date • Trial primary completion date
|
AR (Androgen receptor)
|
AR positive
|
Keytruda (pembrolizumab) • goserelin acetate
6ms
Mucinous metaplasia in Pten conditional knockout mice and mucin family genes as prognostic markers for prostate cancer. (PubMed, Life Sci)
The expression of goblet cell genes, such as MUC1, MUC5AC, MUC5B, and TFF3 have significant prognostic value for PCa patients and represent another class of potential therapeutic targets.
Preclinical • Journal
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PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • MUC1 (Mucin 1) • MUC4 (Mucin 4, Cell Surface Associated) • MUC5B (Mucin 5B, Oligomeric Mucus/Gel-Forming) • MUC19 (Mucin 19, Oligomeric) • MUC5AC (Mucin 5AC) • TFF3 (Trefoil factor 3)
|
AR positive • AR expression • MUC4 expression • MUC5AC expression
6ms
The Incidence of Breast Cancer After Gender-Affirming Mastectomy in Transmen. (PubMed, Ann Plast Surg)
Most documented cases of breast cancer in transmen were diagnosed after gender-affirming surgery, which would suggest residual breast tissue does pose some risk for breast cancer. In addition, those diagnosed with cancer may elect to continue exogenous testosterone therapy despite potential added risks with hormone-receptor positivity. These cases highlight the need for agreement in current screening practices, surgical recommendations, and continuation of masculinizing hormone therapy.Plastic surgeons have the unique opportunity to educate these patients on appropriate breast cancer-related surveillance both before and after chest surgery.
Journal
|
ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
AR positive • ER positive + PGR positive • PGR positive
6ms
Transmembrane 4 L Six Family Member 1 Suppresses Hormone Receptor--Positive, HER2-Negative Breast Cancer Cell Proliferation. (PubMed, Front Pharmacol)
In vivo, the TM4SF1 overexpression inhibited MCF-7 xenograft growth in a nude mouse model, which was associated with the downregulation of the Ki-67 expression, apoptosis induction, and inhibition of the mTOR pathway. TM4SF1 is downregulated in HR + HER2-breast cancer, and the overexpression of TM4SF1 suppresses cell proliferation in this cancer subtype.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor) • IFIT3 (Interferon Induced Protein With Tetratricopeptide Repeats 3) • TM4SF1 (Transmembrane 4 L Six Family Member 1)
|
HER-2 overexpression • HER-2 negative • AR positive • AR expression • TM4SF1 expression • TM4SF1 overexpression
6ms
Taselisib and Enzalutamide in Treating Patients With Androgen Receptor Positive Triple-Negative Metastatic Breast Cancer (clinicaltrials.gov)
P1/2, N=30, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Dec 2021 --> Jul 2022
Trial completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HER-2 negative • AR positive • ER negative • PGR expression • PGR negative
|
enzalutamide capsule • taselisib (GDC-0032)
6ms
The Antitumor Effect of Caffeic Acid Phenethyl Ester by Downregulating Mucosa-Associated Lymphoid Tissue 1 via AR/p53/NF-κB Signaling in Prostate Carcinoma Cells. (PubMed, Cancers (Basel))
CAPE induced the ERK/JNK/p38/AMPKα1/2 signaling pathways; however, pretreatment with the corresponding inhibitors of MAPK or AMPK1/2 did not inhibit the CAPE effect on MALT1 blocking in PC-3 cells. Our findings verify that CAPE is an effective antitumor agent for human androgen-dependent and -independent prostate carcinoma cells in vitro and in vivo through the inhibition of MALT1 expression via the AR/p53/NF-κB signaling pathways.
Journal
|
AR (Androgen receptor) • MALT1 (MALT1 Paracaspase) • KLK3 (Kallikrein-related peptidase 3)
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AR positive • TP53 expression • MALT1 expression
7ms
Clinico-pathological relationship between androgen receptor and tumour infiltrating lymphocytes in triple negative breast cancer. (PubMed, Ecancermedicalscience)
LDBC was associated with higher risk of LN involvement. Larger studies are needed to focus on the clinical impact of the relation between AR and TILs in TNBC.
Journal • Tumor-Infiltrating Lymphocyte
|
AR (Androgen receptor) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
|
AR positive • CD20 expression • CD8 expression • AR expression • CD4 expression
7ms
Mechanistic insights into the selective dual BET and PLK1 inhibitory activity of a novel benzamide compound in castration-resistant prostate cancer. (PubMed, Chem Biodivers)
Consequently, critical interactions peculiar to the oncogenic activities of BRD4 and PLK1 were inhibited, a phenomenon that results in an antagonism of CRPC progression. The mechanistic insights presented in this report would further assist in the structure-based design of improved inhibitors useful in CRPC therapy.
Journal
|
AR (Androgen receptor) • PLK1 (Polo Like Kinase 1) • BRD4 (Bromodomain Containing 4)
|
AR positive
7ms
AR imposes different effects on ZFHX3 transcription depending on androgen status in prostate cancer cells. (PubMed, J Cell Mol Med)
The enzalutamide antiandrogen prevented androgen from inducing ZFHX3 transcription and caused excess ZFHX3 protein degradation. In human PCa, ZFHX3 was downregulated and the downregulation correlated with worse patient survival. These findings establish a regulatory relationship between AR and ZFHX3, suggest a role of ZFHX3 in AR function and implicate ZFHX3 loss in the antiandrogen therapies of PCa.
Journal
|
ZFHX3 (Zinc Finger Homeobox 3)
|
AR positive
|
enzalutamide capsule
7ms
Hsa-mir-3163 and CCNB1 may be potential biomarkers and therapeutic targets for androgen receptor positive triple-negative breast cancer. (PubMed, PLoS One)
The results of current study suggest that CCNB1 and hsa-miR-3163 may serve as highly potential prognostic markers and therapeutic targets for AR positive TNBC. Our findings may make contributions to the diagnosis and therapies of AR positive TNBC.
Journal
|
AR (Androgen receptor) • TOP2A (DNA topoisomerase 2-alpha) • AURKA (Aurora kinase A) • TYMS (Thymidylate Synthetase) • RRM2 (Ribonucleotide Reductase Regulatory Subunit M2) • CCNB2 (Cyclin B2) • CDK1 (Cyclin-dependent kinase 1) • FOXM1 (Forkhead Box M1) • MIR31 (MicroRNA 31) • CCNB1 (Cyclin B1) • CEP55 (Centrosomal Protein 55)
|
AR positive
8ms
QNBC Is Associated with High Genomic Instability Characterized by Copy Number Alterations and miRNA Deregulation. (PubMed, Int J Mol Sci)
Furthermore, the combined expression of these eight miRNAs robustly discriminated TNBCs from QNBCs (AUC = 0.946). Altogether, our results suggest a significant loss of AR in TNBC and a profound impact in genomic instability characterized by CNAs and deregulation of miRNA expression.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
8ms
Clinical Significance of Stromal Tumor-Infiltrating Lymphocytes in Triple Negative Breast Cancer (USCAP 2022)
PD-L1 % IC shows linear correlation with sTILs. Neither PD-L1 nor sTILs levels were significantly associated with survival (RFS, BCSS) in this cohort of patients not subjected to NACT; however, LP-TNBC seems to have good prognosis. Approximately one-half of LP-TNBC showed medullary histology.
Clinical • Tumor-Infiltrating Lymphocyte • PD(L)-1 Biomarker • IO biomarker
|
AR (Androgen receptor)
|
PD-L1 expression • AR positive
|
VENTANA PD-L1 (SP142) Assay
8ms
Triple Negative Breast Cancers Not Subjected to Neoadjuvant Chemotherapy: What’s Prognostic and What’s Not? (USCAP 2022)
High proportion of AR+ TNBC in our cohort suggests that many of these low-grade/low-proliferation TNBCs are not subjected to NACT. Although AR positivity in TNBC is associated with apocrine differentiation, it can also be seen in tumors without apocrine differentiation. AR positivity and not tumor histology was associated with improved RFS.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • AR (Androgen receptor)
|
PD-L1 expression • AR positive
|
VENTANA PD-L1 (SP142) Assay
8ms
Androgen receptor regulates eIF5A2 expression and promotes prostate cancer metastasis via EMT. (PubMed, Cell Death Discov)
We found that eukaryotic translation initiation factor (EIF) 5A2, an elongation factor that induces epithelial-to-mesenchymal transition (EMT) in PCa cells, was significantly upregulated after 5α-dihydrotestosterone (DHT) stimulation and downregulated after anti-androgen bicalutamide treatment in PCa cells with high AR expression, but not in cells with low AR expression...Moreover, in vivo study, Luciferase signals from the lungs of the eIF5A2 plasmid group indicated higher metastasis ability, and the eIF5A2 siRNA group had lower metastasis ability. Our results suggest that AR positively regulates eIF5A2 expression in androgen-dependent cells, and stimulation of AR expression and signaling in prostate tumors promotes PCa metastasis by EMT induction and upregulation of eIF5A2.
Journal
|
AR (Androgen receptor) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CDH1 (Cadherin 1) • VIM (Vimentin)
|
AR positive • AR expression • CDH1 expression • AR underexpression • VIM expression
|
bicalutamide
8ms
Understanding and targeting prostate cancer cell heterogeneity and plasticity. (PubMed, Semin Cancer Biol)
I further elaborate on PCa cell plasticity induced by genetic alterations and therapeutic interventions, and present potential strategies to therapeutically tackle PCa cell heterogeneity and plasticity. My discussions will make it clear that, to achieve enduring clinical efficacy, both intrinsic PCa cell heterogeneity and induced PCa cell plasticity need to be targeted with novel combinatorial approaches.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
9ms
Cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with ralaniten analogues for the treatment of androgen receptor-positive prostate and breast cancers. (PubMed, Mol Cancer Ther)
Androgen receptor (AR) has essential roles in the growth of prostate cancer and some breast cancers. Importantly, sequential combination treatments with palbociclib administered first then followed by EPI-7170, resulted in more cells accumulating in G1 and less cells in S phase than concomitant combination which was presumably because each inhibitor has a unique mechanism in modulating the cell cycle in cancer cells. Together these data support that the combination therapy was more effective than individual monotherapies to reduce tumor growth by targeting different phases of the cell cycle.
Journal • Combination therapy
|
AR (Androgen receptor)
|
AR positive
|
Ibrance (palbociclib) • EPI-7170 • ralaniten acetate (EPI-506)
9ms
Phase II study of enzalutamide in androgen receptor positive, recurrent, high- and low-grade serous ovarian cancer. (PubMed, Gynecol Oncol)
The study met its primary endpoint, with a PFS rate of 22% (n = 13); however, the overall response rate was low. Enzalutamide was well tolerated and may be a potential treatment option in select patients.
P2 data • Journal
|
AR (Androgen receptor)
|
AR positive
|
enzalutamide capsule
9ms
Anti-Androgen Therapy Radiosensitizes Androgen Receptor Positive Cancers to F-18 Fluorodeoxyglucose. (PubMed, J Nucl Med)
Bicalutamide (Bical), an anti-androgen drug, was identified to share similar toxicity in combination with either F-FDG or X-rays, indicating its sensitivity as a radiosensitizer to F-FDG...Histopathology corroborated the in vitro and in vivo data and confirmed the absence of off-target toxicity to vital organs. These data provide evidence that F-FDG in conjunction with anti-androgens serving as radiosensitizers has utility as a radiotherapeutic agent in the ablation of AR-positive cancers.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
|
bicalutamide
9ms
Study on Androgen Receptor and Triple Negative Breast Cancer (clinicaltrials.gov)
P2, N=94, Active, not recruiting, UNICANCER | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Jun 2023
Clinical • Enrollment closed • Trial completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HER-2 negative • AR positive
|
capecitabine • Nubeqa (darolutamide)
9ms
Secreted indicators of androgen receptor activity in breast cancer pre-clinical models. (PubMed, Breast Cancer Res)
KLK3, AZGP1 and PIP are AR regulated and reflect tumor AR activity. Further investigations are needed to examine the potential efficacy of these factors as serum biomarkers.
Preclinical • Journal
|
AR (Androgen receptor) • AZGP1 (Alpha-2-Glycoprotein 1, Zinc-Binding) • KLK3 (Kallikrein-related peptidase 3)
|
AR positive
|
enzalutamide capsule
9ms
A biomarker study in Peruvian males with breast cancer. (PubMed, World J Clin Oncol)
Male BC is usually ER and AR positive, and Luminal-A. MMR loss and PIK3CA mutations are infrequent. Stage and grade predicted overall survival in our South American country population.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AR (Androgen receptor)
|
ER positive • PIK3CA mutation • HER-2 negative • PIK3CA H1047R • AR positive • AR expression
10ms
Identification of a selective BRD4 PROTAC with potent antiproliferative effects in AR-positive prostate cancer based on a dual BET/PLK1 inhibitor. (PubMed, Eur J Med Chem)
Moreover, WWL0245 induced cell cycle arrest at the G0/G1 phase and apoptosis in AR-positive prostate cancer by downregulation of the protein levels of AR, PSA and c-Myc as well as transcriptionally suppressed AR-regulated genes. WWL0245 was thus expected to be developed as a promising drug candidate for AR-positive prostate cancer and a valuable tool compound to study the biological function of BRD4.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AR (Androgen receptor) • BRD4 (Bromodomain Containing 4)
|
AR positive
10ms
Identification of AR driven tumors within TNBC using a novel gene signature (SABCS 2021)
Conclusion Identification of AR driven tumors within TNBC has both prognostic and predictive utility. Methods using limited number of AR regulated genes could be easily applied to larger BC cohorts to identify TNBC tumours driven by AR signalling and may respond well to anti-androgen therapies.
Gene Signature
|
ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FOXA1 (Forkhead Box A1) • ITK (IL2 Inducible T Cell Kinase) • SOCS2 (Suppressor Of Cytokine Signaling 2) • GATA3 (GATA binding protein 3) • TFF1 (Trefoil Factor 1)
|
TP53 mutation • PIK3CA mutation • AR positive • AR expression • ER overexpression • EMT gene signature
|
TNBCType-IM assay
10ms
Adjuvant enzalutamide for the treatment of early-stage androgen-receptor positive, triple negative breast cancer: A feasibility study (SABCS 2021)
Of those who did not achieve a pCR, 69% received adjuvant capecitabine. This single-arm trial previously met its primary endpoint of feasibility in patients with early-stage AR+ TNBC. In this relatively high-risk, albeit highly selected patient population, the 3-year DFS measured 80% (95% CI: 67 - 94%) with an adjuvant endocrine therapy approach. Efforts to determine the optimal biomarker for AR+ TNBC are ongoing, so that patients most likely to respond to AR-antagonists in both the early and metastatic setting may be identified.
Clinical • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • AR (Androgen receptor) • PALB2 (Partner and localizer of BRCA2)
|
HER-2 negative • PALB2 mutation • AR positive • AR expression
|
capecitabine • enzalutamide capsule
10ms
Androgen receptor as predictive marker for pathologic complete response in breast cancer with neoadjuvant chemotherapy (SABCS 2021)
This study shows that AR expression is predominant in luminal A subtype. When determining neoadjuvant chemotherapy in luminal A subtype, AR expression can be considered as a pCR predictive marker.
Clinical
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HER-2 positive • AR positive • ER negative • AR expression
10ms
Treatment patterns and outcomes of palliative systemic therapy in patients with salivary duct carcinoma and adenocarcinoma, not otherwise specified. (PubMed, Cancer)
Adding systemic therapy to local therapy may improve outcomes of patients with locoregionally advanced SDC or adeno-NOS. Except for HER2-targeted therapy, response to palliative systemic therapy is limited. These findings may be used as a benchmark for future drug development.
Clinical • Journal
|
AR (Androgen receptor)
|
HER-2 positive • AR positive
|
Herceptin (trastuzumab)
10ms
Expression and clinical implications of basic leucine zipper ATF-like transcription factor 2 in breast cancer. (PubMed, BMC Cancer)
BC patients exhibit low-to-moderate expressions in BATF2 mRNA expression levels in cancerous tissues. The high BATF2 protein expression can be a potential indicator of a better BC prognosis. Serum and exosomal BATF2 mRNA levels also serve as promising noninvasive biomarkers for BC diagnosis.
Clinical • Journal • BRCA Biomarker
|
TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • AR (Androgen receptor) • MKI67 (Marker of proliferation Ki-67)
|
AR positive • TP53 expression
10ms
Activity of preclinical and phase I clinical trial of a novel androgen receptor antagonist GT0918 in metastatic breast cancer. (PubMed, Breast Cancer Res Treat)
GT0918 can effectively inhibit AR-positive breast cancer tumor growth. GT0918 was demonstrated well tolerated with a favorable PK profile. The suitable dose of GT0918 was 500 mg QD and may provide clinical benefits for AR-positive mBC.
P1 data • Preclinical • Clinical Trial,Phase I • Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
|
proxalutamide (GT0918)
10ms
Ribociclib and Bicalutamide in AR+ TNBC (clinicaltrials.gov)
P1/2, N=37, Active, not recruiting, Kari Wisinski | Trial completion date: Sep 2022 --> Sep 2024 | Trial primary completion date: Sep 2021 --> Sep 2023
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AR (Androgen receptor)
|
HER-2 negative • AR positive
|
Kisqali (ribociclib) • bicalutamide
10ms
A phase II study of dual immune checkpoint blockade (ICB) plus bicalutamide to enhance thymic T-cell production and immunotherapy response in metastatic breast cancer (MBC) (SABCS 2021)
Dual ICB with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) has not been studied in depth in MBC despite its success in other solid tumors. Contact: Dr . David Page (David.page2@providence.org) Clinicaltrials.gov#: NCT03650894
P2 data • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
|
AR (Androgen receptor)
|
PD-L1 expression • HR positive • PD-L1 negative • AR positive • AR expression
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • bicalutamide
10ms
GLI3 is stabilized by SPOP mutations and promotes castration resistance via functional cooperation with androgen receptor in prostate cancer. (PubMed, Mol Cancer Res)
Together, these findings reveal that hyperactivated GLI3 promotes castration-resistant growth of prostate cancer and provide a rationale for therapeutic targeting of GLI3 in CRPC patients. Implications: We describe two clinically relevant mechanisms leading to hyperactivated GLI3 signaling and enhanced AR/GLI3 crosstalk, suggesting that GLI3-specific inhibitors might prove effective to block prostate cancer development or delay CRPC.
Journal
|
AR (Androgen receptor) • GLI3 (GLI Family Zinc Finger 3) • SPOP (Speckle Type BTB/POZ Protein)
|
AR positive • SPOP mutation
10ms
Clinical • Enrollment open
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AR (Androgen receptor)
|
ER positive • HER-2 negative • AR positive
|
everolimus • fulvestrant • exemestane • Ostarine (enobosarm)
10ms
Clinical • New P2 trial
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AR (Androgen receptor)
|
ER positive • HER-2 negative • AR positive
|
Ibrance (palbociclib) • everolimus • Verzenio (abemaciclib) • fulvestrant • exemestane • Ostarine (enobosarm)
10ms
Abiraterone Acetate in Patients With Castration-Resistant, Androgen Receptor-Expressing Salivary Gland Cancer: A Phase II Trial. (PubMed, J Clin Oncol)
Abiraterone plus luteinizing hormone-releasing hormone agonist is active and safe as a second-line option in AR-expressing, castration-resistant SGC.
Clinical • P2 data • Journal
|
AR (Androgen receptor)
|
AR positive • AR overexpression • AR expression
|
abiraterone acetate • prednisone
10ms
A phase II study of nivolumab, ipilimumab, plus androgen receptor blockade with bicalutamide to enhance thymic T-cell production and immunotherapy response in metastatic breast cancer (SITC 2021)
Biomarkers of recent thymic activation will be evaluated via quantitative deep sequencing of T-cell receptors (TcR, ImmunoSEQ assay), TcR excision circles (TRECs), and flow cytometry using markers for recent thymic emigration (CD3+CD45RA+CD45RO-CD31+) Trial Registration NCT03650894. The trial is open at Providence Cancer Institute (Portland, OR) and Memorial Sloan Kettering Cancer Center (New York, NY).
P2 data • PD(L)-1 Biomarker • IO biomarker
|
AR (Androgen receptor) • CD31 (Platelet and endothelial cell adhesion molecule 1)
|
PD-L1 expression • HR positive • PD-L1 negative • AR positive • AR expression
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • bicalutamide
11ms
Safety, Tolerability, and Pharmacokinetics of Proxalutamide Therapy in Women With Metastatic Breast Cancer (clinicaltrials.gov)
P1, N=63, Completed, Suzhou Kintor Pharmaceutical Inc, | Active, not recruiting --> Completed
Clinical • Trial completion
|
AR (Androgen receptor)
|
AR positive
|
proxalutamide (GT0918)
11ms
4CAST: Seviteronel in Combination With Chemotherapy in Androgen-receptor Positive Metastatic Triple-negative Breast Cancer (clinicaltrials.gov)
P1b, N=65, Not yet recruiting, St Vincent's Hospital, Sydney | Initiation date: Jul 2021 --> Nov 2021
Clinical • Trial initiation date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HR positive • HER-2 negative • AR positive
|
docetaxel • dexamethasone • seviteronel (INO-464)
11ms
Apocrine lesions of the breast. (PubMed, Virchows Arch)
HER-2 status may be positive or negative. This article reviews the pathology of benign, atypical and malignant apocrine lesions of the breast, with emphasis on diagnostic criteria including an approach to evaluation of apocrine lesions on needle core biopsy, and recent advances in our understanding of invasive apocrine carcinoma.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
AR positive • HR negative • AR expression • PGR negative
11ms
Development of a Benzothiazole Scaffold-Based Androgen Receptor N-Terminal Inhibitor for Treating Androgen-Responsive Prostate Cancer. (PubMed, ACS Chem Biol)
We describe the identification of 2-(4-fluorophenyl)-5-(trifluoromethyl)-1,3-benzothiazole (A4B17), a small molecule that inhibits BAG1L-AR NTD interaction, attenuates BAG1L-mediated AR NTD activity, downregulates AR target gene expression, and inhibits proliferation of AR-positive prostate cancer cells. This compound represents a prototype of AR antagonists that could be key in the development of future prostate cancer therapeutics.
Journal
|
AR (Androgen receptor)
|
AR positive
11ms
AR-negative prostate cancer is vulnerable to loss of JMJD1C demethylase. (PubMed, Proc Natl Acad Sci U S A)
Correspondingly, AR-negative prostate cancer cells showed exquisite sensitivity to TNFα treatment and, conversely, TNFα pathway inhibition via inhibition of its downstream effector MAP4K4 partially reversed the growth defect of JMJD1C-depleted AR-negative prostate cancer cells. Given the deleterious systemic side effects of TNFα therapy in humans and the viability of JMJD1C-knockout mice, the identification of JMJD1C inhibition as a specific vulnerability in AR-negative prostate cancer may provide an alternative drug target for prostate cancer patients progressing on AR inhibitor therapy.
Journal
|
AR (Androgen receptor)
|
AR positive
11ms
Use of FVB Myc-CaP cells as an immune competent, androgen receptor positive, mouse model of prostate cancer bone metastasis. (PubMed, J Bone Oncol)
However, conditioned media from Myc-CaP cells stimulated osteoclast formation in vitro from FVB/NJ mouse bone marrow. Overall, Myc-CaP cells injected in the left ventricle or tibia of syngeneic mice recapitulate key aspects of human metastatic PCa.
Preclinical • Journal
|
AR (Androgen receptor)
|
AR positive
11ms
MiR-205-driven downregulation of cholesterol biosynthesis through SQLE-inhibition identifies therapeutic vulnerability in aggressive prostate cancer. (PubMed, Nat Commun)
Furthermore, SQLE was essential for proliferation of AR-positive PCa cell lines, including abiraterone or enzalutamide resistant derivatives, and blocked transactivation of the AR pathway. Finally, terbinafine reduced levels of prostate specific antigen (PSA) in three out of four late-stage PCa patients. These results highlight SQLE as a therapeutic target for the treatment of advanced PCa.
Journal
|
AR (Androgen receptor) • MIR205 (MicroRNA 205)
|
AR positive
|
enzalutamide capsule • abiraterone acetate • terbinafine HCL
11ms
[VIRTUAL] RETROSPECTIVE COHORT STUDY OF OUTCOMES FOR TRANSGENDER AND GENDER DIVERSE PEDIATRIC AND YOUNG ADULT PATIENTS WITH CANCER (SIOP 2021)
Oncology providers will benefit from more education regarding caring for transgender patients, including correct pronoun usage. Transgender pediatric patients with cancer undergo treatments or suffer from toxicities that may affect GAC, highlighting the need for multidisciplinary care. Future studies need to incorporate experiences of transgender pediatric patients with cancer to further improve care.
Retrospective data
|
AR (Androgen receptor)
|
AR positive
11ms
Structural and biophysical insights into the mode of covalent binding of rationally designed potent BMX inhibitors. (PubMed, RSC Chem Biol)
The new inhibitors displayed anti-proliferative effects in androgen-receptor positive prostate cancer cells that where further increased when combined with known inhibitors of related signaling pathways, such as PI3K, AKT and Androgen Receptor. We expect these findings to guide development of new selective BMX therapeutic approaches.
Journal
|
AR (Androgen receptor)
|
AR positive
12ms
Discovery and Characterization of Benzimidazole Derivative XY123 as a Potent, Selective, and Orally Available RORγ Inverse Agonist. (PubMed, J Med Chem)
Significantly, oral administration of compound 27h achieved complete and long-lasting tumor regression in the 22Rv1 xenograft tumor model in mice. Compound 27h may serve as a new valuable lead compound for further development of drugs for the treatment of prostate cancer.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
12ms
The importance of androgen receptors in breast cancer. (PubMed, Med Pharm Rep)
AR is a potential targeted pathway which can improve the prognostic of AR positive patients with BC. Further preclinical and clinical studies are necessary to clarify the mechanism of action and to establish the drugs which can be used, either alone or in combination.
Review • Journal
|
AR (Androgen receptor)
|
AR positive
12ms
YATAGARASU: A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma (clinicaltrials.gov)
P2, N=31, Active, not recruiting, Janssen Pharmaceutical K.K. | Trial completion date: Oct 2022 --> Jan 2023
Clinical • Trial completion date • Combination therapy
|
AR (Androgen receptor)
|
AR positive • AR expression
|
Erleada (apalutamide) • goserelin acetate
12ms
CX-5461 sensitises DNA damage repair proficient castrate-resistant prostate cancer to PARP inhibition. (PubMed, Mol Cancer Ther)
Therefore, combination treatment with CX-5461 and talazoparib is effective for HR-proficient tumours that are not suitable for monotherapy with PARP inhibitors, including AR-null CRPC. This expands the spectrum of CRPC that is sensitive to PARP inhibition.
Journal
|
AR (Androgen receptor)
|
AR positive
|
Talzenna (talazoparib) • pidnarulex (CX-5461)
1year
Enzalutamide Enhances PSMA Expression of PSMA-Low Prostate Cancer. (PubMed, Int J Mol Sci)
Enzalutamide induced PSMA expression in the 22Rv1 xenograft model and in an mCRPC patient, both with low baseline tumoral PSMA levels. Therefore, enzalutamide pre-treatment might render patients with low PSMA expression eligible for Lu-PSMA RLT.
Journal
|
AR (Androgen receptor) • FOLH1 (Folate hydrolase 1)
|
AR positive • AR expression • FOLH1 expression
|
enzalutamide capsule
1year
[VIRTUAL] Androgen Deprivation Therapy for Advanced or Recurrent Salivary Gland Carcinoma: A Systematic Review (AHNS 2021)
Existing data for the use of ADT in advanced SGC is promising. Further optimization and standardization of protocols is needed, ideally in the form of prospective controlled trials.
Review
|
AR (Androgen receptor)
|
AR positive
1year
Inhibition of Janus Kinase 1 synergizes docetaxel sensitivity in prostate cancer cells. (PubMed, J Cell Mol Med)
Furthermore, inhibition of JAK1/2 by baricitinib and ruxolitinib synergizes docetaxel sensitivity in both androgen receptor (AR)-negative DU145 and PC3 cells, but not in the AR-positive LNCaP cells. In contrast, no synergistic effects were observed in cells treated with JAK2-specific inhibitor, fedratinib, suggesting that the synergistic effects are mainly mediated through JAK1 inhibition. In conclusion, the combination therapy with JAK1 inhibitors and docetaxel could be a useful therapeutic strategy in the treatment of prostate cancers.
Journal
|
AR (Androgen receptor) • JAK1 (Janus Kinase 1)
|
AR positive
|
docetaxel • Jakafi (ruxolitinib) • Inrebic (fedratinib) • Olumiant (baricitinib)
1year
RNA splicing factors SRRM3 and SRRM4 distinguish molecular phenotypes of castration-resistant neuroendocrine prostate cancer. (PubMed, Cancer Res)
Two AMPC phenotypes and three SCNPC phenotypes were characterized, denoted either by REST attenuation and ASCL1 activity or by progressive activation of neuronal transcription factor programs, respectively. These results nominate SRRM3 as the principal REST splicing factor expressed in early NE differentiation and provide a framework to molecularly classify diverse NE phenotypes in mCRPC.
Journal
|
AR (Androgen receptor)
|
AR positive
1year
α-Methylacyl-CoA racemase: a useful immunohistochemical marker of breast carcinoma with apocrine differentiation. (PubMed, Hum Pathol)
In selected cases, AMACR mRNA levels were quantitatively determined relative to that of TATA-binding protein mRNA, and they comprised 5.23, 1.33, and 0.60 for carcinomas with apocrine differentiation, non-apocrine carcinomas, and normal breast tissue, respectively. Our findings demonstrate that AMACR expression may be utilized for differentiating carcinoma with apocrine differentiation from non-apocrine carcinomas and indicate that AMACR is a more sensitive carcinoma with apocrine differentiation marker than GCDFP-15.
Journal
|
AR (Androgen receptor)
|
AR positive
1year
Predictive and Prognostic Biomarker Identification in a Large Cohort of Androgen Receptor-Positive Salivary Duct Carcinoma Patients Scheduled for Combined Androgen Blockade. (PubMed, Cancers (Basel))
mRNA from 76 R/M androgen receptor (AR)-positive SDC patients treated with leuprorelin acetate combined with bicalutamide was extracted from pre-treatment tumor specimens...SRD5A1 expression can identify patients that will and AR PAS patients that will not experience clinical benefit (85.7% and 93.3% for PPV and NPV, respectively). The predictive potential of SRD5A1 expression forms a rational basis for including SRD5A1-inhibitors in SDC patients' treatment.
Clinical • Journal
|
ER (Estrogen receptor) • AR (Androgen receptor) • TGFB1 (Transforming Growth Factor Beta 1)
|
AR positive
|
bicalutamide
1year
Prognostic value of androgen receptor expression and molecular alterations in metastatic triple negative or low hormone receptor breast carcinomas. (PubMed, Hum Pathol)
In addition, AR-positive tumors had significantly higher rate of PI3CA mutation. Our results demonstrated that AR expression has prognostic value in this subgroup of metastatic BCs and tumors with AR expression had different molecular alterations compared to those without AR expression.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
AR positive • AR expression
1year
Suppression of bone metastatic castration-resistant prostate cancer cell growth by a suicide gene delivered by JC polyomavirus-like particles. (PubMed, Gene Ther)
To further investigate whether PSAtk-VLPs inhibit the growth of metastasized prostate cancer cells, we established an animal model of bone-metastatic prostate cancer to compare PSAtk-VLPs with leuprorelin acetate and enzalutamide, hormonal agents commonly used in clinical settings, and investigated the effectiveness of PSAtk-VLPs...In addition, PSAtk-VLPs showed a higher effectiveness than hormone therapy in this animal model study. These results suggest that PSAtk-VLPs may serve as a treatment option for mCRPC therapy in the future.
Journal
|
AR (Androgen receptor)
|
AR positive
|
enzalutamide capsule
1year
[VIRTUAL] Case series of docetaxel, trastuzumab, and pertuzumab (DTP) and subsequent ado-trastuzumab emtansine (T-DM1) for recurrent or metastatic (R/M) HER2-positive salivary duct carcinoma (SDC) (ESMO 2021)
In R/M HER2-positive SDC patients DTP followed by T-DM1 upon progression are promising treatment strategies, leading to responses in the majority of the patients at an acceptable toxicity profile. The median OS was not reached after a median follow-up of 15.4 months.
Clinical
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
|
HER-2 positive • AR positive
|
Herceptin (trastuzumab) • docetaxel • Kadcyla (ado-trastuzumab emtansine) • Perjeta (pertuzumab)
1year
[VIRTUAL] ARB: Phase II window of opportunity study of preoperative treatment with enzalutamide in ER+ve and TNBC (ESMO 2021)
No difference was seen overall in inhibition of Ki67 expression after treatment with enz. However, subgroup analysis did show a possible response in LumA pts.
P2 data
|
ER (Estrogen receptor) • AR (Androgen receptor) • CASP3 (Caspase 3)
|
ER positive • AR positive • AR expression
|
enzalutamide capsule
1year
Stage-specific Embryogenic Antigen-4 Expression in Castration-resistant Prostate Cancer and its Correlation With the Androgen Receptor. (PubMed, Anticancer Res)
SSEA-4 was over-expressed in CRPC and the changes were mediated by complex mechanisms that related to the AR and hormonal therapy.
Journal
|
AR (Androgen receptor)
|
AR positive
1year
Selective inhibition of the second bromodomain of BET family proteins results in robust antitumor activity in preclinical models of acute myeloid leukemia. (PubMed, Mol Cancer Ther)
Studies in AML xenograft models demonstrated anti-tumor efficacy for ABBV-744 that was comparable to the pan-BET inhibitor ABBV-075 but with an improved therapeutic index. Enhanced anti-tumor efficacy was also observed with the combination of ABBV-744 and the BCL-2 inhibitor, venetoclax compared to monotherapies of either agent alone. These results collectively support the clinical evaluation of ABBV-744 in AML (Clinical Trials.gov identifier: NCT03360006).
Preclinical • Journal
|
AR (Androgen receptor) • BRD4 (Bromodomain Containing 4)
|
AR positive
|
Venclexta (venetoclax) • ABBV-744 • mivebresib (ABBV 075)
1year
Periocular apocrine adenocarcinoma presenting as an orbital mass: clinicopathological features and management in four patients. (PubMed, Eur J Ophthalmol)
The fourth patient had to be managed with oral bicalutamide which kept the tumor stable for 3 years...Orbital exenteration appeared as an effective treatment of apocrine adenocarcinoma with orbital extension. Anti-androgenic treatment in an androgen receptor-positive tumor provided temporary local tumor control.
Clinical • Journal
|
AR (Androgen receptor)
|
AR positive
|
bicalutamide
1year
Clinical • New P1 trial • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HR positive • HER-2 negative • AR positive
|
docetaxel • dexamethasone • seviteronel (INO-464)
1year
Temporal evolution of cellular heterogeneity during the progression to advanced AR-negative prostate cancer. (PubMed, Nat Commun)
Moreover, global DNA methylation and the N-Myc cistrome are redirected following Rb1 loss. Altogether, our data provide insight into the progression of prostate adenocarcinoma to NEPC.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AR (Androgen receptor) • RB1 (RB Transcriptional Corepressor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor)
|
AR positive • MYC overexpression • MYC expression
1year
Bicalutamide in Treating Patients With Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=28, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Mar 2022 --> Jun 2021 | Trial primary completion date: Mar 2022 --> Jun 2021
Clinical • Trial completion • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
AR positive • PGR negative
|
bicalutamide
1year
YATAGARASU: A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma (clinicaltrials.gov)
P2, N=31, Active, not recruiting, Janssen Pharmaceutical K.K. | Trial completion date: Jul 2021 --> Oct 2022
Clinical • Trial completion date • Combination therapy
|
AR (Androgen receptor)
|
AR positive • AR expression
|
Erleada (apalutamide) • goserelin acetate
1year
Androgen Receptor is Expressed in Breast Cancer Brain Metastases. (PubMed, Appl Immunohistochem Mol Morphol)
AR is expressed in more than one third of BC BM with the highest rates among the luminal/HER2-negative BC subtype and may therefore be a potential prognostic and predictive biomarker in this particular BC population.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
|
HER-2 positive • HER-2 negative • AR positive • AR expression
1year
FOXA1 overexpression suppresses interferon signaling and immune response in cancer. (PubMed, J Clin Invest)
These findings were also validated in bladder cancer expressing high level FOXA1. FOXA1 overexpression could be a prognostic factor to predict therapy resistance and a viable target to sensitize luminal prostate, breast and bladder cancer to immuno- and chemotherapy.
Journal • IO biomarker
|
ER (Estrogen receptor) • AR (Androgen receptor) • FOXA1 (Forkhead Box A1) • STAT2 (Signal transducer and activator of transcription 2)
|
ER positive • AR positive • FOXA1 overexpression
1year
Chemical Degradation of Androgen Receptor (AR) Using Bicalutamide Analog-Thalidomide PROTACs. (PubMed, Molecules)
A series of PROTACs (PROteolysis-TArgeting Chimeras) consisting of bicalutamide analogs and thalidomides were designed, synthesized, and biologically evaluated as novel androgen receptor (AR) degraders. In particular, we found that PROTAC compound 13b could successfully demonstrate a targeted degradation of AR in AR-positive cancer cells and might be a useful chemical probe for the investigation of AR-dependent cancer cells, as well as a potential therapeutic candidate for prostate cancers.
Clinical • Review • Journal
|
AR (Androgen receptor)
|
AR positive
|
thalidomide • bicalutamide
1year
Androgen receptor expression in breast cancer: implications on prognosis and treatment, a brief review. (PubMed, Mol Cell Endocrinol)
Studies of biomarkers to identify the patients likely to benefit from AR-targeted therapies are currently in progress. Besides, AR expression may be an important prognostic and predictive marker for breast cancer, which needs to be defined better in future studies.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AR (Androgen receptor)
|
HER-2 expression • AR positive • AR expression • ER expression
1year
Expression of G3BP1 in benign and malignant human prostate tissues. (PubMed, Transl Androl Urol)
Besides, G3BP1 might be associated with biochemical recurrence. These results supply potential target for the management of the PCa.
Journal
|
AR (Androgen receptor) • G3BP1 (G3BP Stress Granule Assembly Factor 1)
|
AR positive • AR expression
over1year
Clinical • New P3 trial
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AR (Androgen receptor)
|
ER positive • HER-2 negative • AR positive
|
everolimus • fulvestrant • exemestane • Ostarine (enobosarm)
over1year
Clinical Implications of Androgen-Positive Triple-Negative Breast Cancer. (PubMed, Cancers (Basel))
AR antagonists are a promising novel therapeutic approach in AR-positive TNBC. However, AR signaling pathways should be more investigated in order to understand the influence of AR expression on TNBC more thoroughly.
Clinical • Review • Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
over1year
Comparison of Androgen Receptor, VEGF, HIF-1, Ki67 and MMP9 Expression between Non-Metastatic and Metastatic Stages in Stromal and Tumor Cells of Oral Squamous Cell Carcinoma. (PubMed, Life (Basel))
Our results show for the first time an interplay between AR, VEGF, MMP9, HiF1beta and Ki67 in OSCC which may contribute to better diagnostics and therapy selection.
Journal
|
AR (Androgen receptor) • VEGFA (Vascular endothelial growth factor A) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • MMP9 (Matrix metallopeptidase 9) • ARNT (Aryl Hydrocarbon Receptor Nuclear Translocator)
|
AR positive • HIF1A expression
over1year
[VIRTUAL] A phase Ib study of proxalutamide (GT0918) in women with androgen receptor-positive metastatic breast cancer. (ASCO 2021)
GT0918 has been shown to be well tolerated and may provide potential clinical benefits to AR positive metastatic breast cancer patients . This study demonstrated triple negative in AR positive patients had more benefit.
Clinical • P1 data
|
AR (Androgen receptor)
|
AR positive
|
proxalutamide (GT0918)
over1year
[VIRTUAL] Efficacy of enobosarm, a selective androgen receptor (AR) targeting agent, correlates with the degree of AR positivity in advanced AR+/estrogen receptor (ER)+ breast cancer in an international phase 2 clinical study. (ASCO 2021)
Enobosarm is a novel oral selective AR activating agent in which a higher % AR staining correlates with a greater antitumor activity . By targeting and activating AR, enobosarm may represent a new hormone treatment approach for AR+/ER+ MBC . The phase 3, ARTEST trial will commence in early 2021 and randomize patients with AR+/ER+/HER2- heavily treated MBC that have progressed on a non-steroidal aromatase inhibitor, fulvestrant and CDK 4/6 inhibitor to receive enobosarm or standard endocrine therapy.
Clinical • P2 data
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AR (Androgen receptor)
|
HER-2 negative • AR positive • AR expression
|
fulvestrant • Ostarine (enobosarm)
over1year
YATAGARASU: A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma (clinicaltrials.gov)
P2, N=31, Active, not recruiting, Janssen Pharmaceutical K.K. | Trial primary completion date: Mar 2021 --> Jun 2021
Clinical • Trial primary completion date • Combination therapy
|
AR (Androgen receptor)
|
AR positive • AR expression
|
Erleada (apalutamide) • goserelin acetate
over1year
Bicalutamide in Treating Patients With Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=28, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2021 --> Mar 2022 | Trial primary completion date: Mar 2021 --> Mar 2022
Clinical • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
AR positive • PGR negative
|
bicalutamide
over1year
Neuroendocrine cells of the prostate: Histology, biological functions, and molecular mechanisms. (PubMed, Precis Clin Med)
In this article, we review the morphology and function of NE cells in benign prostate and PCa as well as underlying molecular mechanisms. In addition, we review the major reported mechanisms for transformation from common adenocarcinoma histology to the highly lethal SCNC, a significant clinical challenge in the management of advanced PCa.
Review • Journal
|
AR (Androgen receptor)
|
AR positive
over1year
Differential Expression of Androgen Receptor in Type I and Type II Endometrial Carcinomas: A Clinicopathological Analysis and Correlation with Outcome. (PubMed, Oman Med J)
AR expression was not significantly correlated with age, stage, ER, atypical hyperplasia, recurrence, node status, or outcome. Results agree with recent literature that AR expression is associated with better-differentiated EC and may be a potential hormonal therapeutic tool.
Clinical • Journal
|
ER (Estrogen receptor) • AR (Androgen receptor)
|
AR positive • AR expression • ER expression
over1year
Androgen receptor signalling confers clonogenic and migratory advantages in urothelial cell carcinoma of the bladder. (PubMed, Mol Oncol)
In an AR-positive UCC-derived cell line model, UM-UC-3-AR, androgen treatment increased clonogenic capacity inducing the formation of big stem cell-like holoclones, while AR knockdown or treatment with the AR antagonist Enzalutamide abrogated this clonogenic advantage...These phenotypic changes were accompanied by a rewiring of the transcriptome with almost 300 genes being differentially regulated by androgens, some of which correlated with AR expression in UCC patients in two independent data sets. Our results demonstrate that AR signals in UCC favouring the development of an aggressive phenotype and highlights its potential as a therapeutic target for bladder cancer.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
|
enzalutamide capsule
over1year
Androgen receptor decreases renal cell carcinoma bone metastases via suppressing the osteolytic formation through altering a novel circEXOC7 regulatory axis. (PubMed, Clin Transl Med)
These data showed that AR/DHX9/circEXOC7/miR-149-3p/CSF1 signaling acts as a valuable feature in the bone metastasis of renal cancer, which may benefit in suppressing the RBM progression.
Journal
|
AR (Androgen receptor) • CSF1 (Colony stimulating factor 1)
|
AR positive • AR expression • CSF1 expression
over1year
[VIRTUAL] Preclinical Evidence of the Efficacy of Lewis Y Car T Cells in Patient-Derived Models of Prostate Cancer (ENDO 2021)
However, CAR T cells given after a single dose of the chemotherapeutic agent carboplatin greatly and durably reduced tumour burden, with residual tumour mass being less than 1% of their original size (0.56 ± 0.23% of tumour volume at the start of treatment)...For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021.
Preclinical • CAR T-Cell Therapy • IO biomarker
|
AR (Androgen receptor) • GZMB (Granzyme B)
|
AR positive • AR expression
|
carboplatin
over1year
Triple-negative breast lobular carcinoma: a luminal androgen receptor carcinoma with specific ESRRA mutations. (PubMed, Mod Pathol)
Our findings highlight that TN-ILC is a unique aggressive breast cancer associated with elderly age, which belong to the luminal androgen receptor subtype as determined by immunohistochemistry and transcriptomic profiling. Moreover, it harbors specific molecular alterations (PI3K, ERBB2 and ESRRA) which may pave the way for new targeted therapeutic strategies.
Journal
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor) • SOX10 (SRY-Box 10)
|
HR positive • HER-2 expression • EGFR expression • AR positive
over1year
A novel 1-((3-(2-toluyl)-4,5-dihydroisoxazol-5-yl)methyl)-4-(trifluoromethyl)pyrimidin-2(1H)-one activates intrinsic mitochondria-dependent pathway and decreases angiogenesis in PC-3 cells. (PubMed, Eur J Pharmacol)
The compound also led PC-3 to lipid peroxidation and mitochondrial depolarization which triggered the activation of intrinsic pathway, confirmed by increase of cleaved caspase-9 and 3. In this work we also show the ability of 9c in reducing vascular endothelial growth factor expression (VEGF) and inhibiting topoisomerase I enzyme, therefore indicating a potential new molecule to be further investigated for prostate cancer management.
Journal
|
AR (Androgen receptor) • CASP9 (Caspase 9)
|
AR positive • VEGFA expression
over1year
Activity of combined androgen receptor antagonism and cell cycle inhibition in androgen receptor-positive triple-negative breast cancer. (PubMed, Mol Cancer Ther)
The purpose of this study was to investigate the pre-clinical activity of the CDK4/6 inhibitor abemaciclib in combination with an agent that targets both androgen biosynthesis and AR activity, seviteronel, using TNBC cell lines expressing high AR, cell line xenografts and an AR positive, androgen-responsive TNBC patient-derived xenograft (PDX). Implications. While cell cycle inhibitors are FDA-approved for use in ER-positive breast cancer, our studies suggest that they may also be effective in AR+ TNBC, perhaps combined with AR targeted agents.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
ER positive • HER-2 amplification • AR positive
|
Verzenio (abemaciclib) • seviteronel (INO-464)
over1year
A Dual-Surgeon Approach to Breast Cancer Surgery in a Transmale. (PubMed, Ann Plast Surg)
The patient did not require adjuvant chemotherapy or radiation but was started on adjuvant hormone therapy targeting his hormone receptor positive cancer. He elected to stay on low-dose masculinizing hormone therapy with continued surveillance examinations.We follow our case with a review of the current literature involving breast cancer in transmales to explore current screening practices, surgical recommendations, adjuvant therapies, continuation of masculinizing hormone therapy, and postoperative surveillance guidelines in the hopes of informing plastic surgeons in having these discussions with their transmale patients and thus improving informed cancer care for this population.
Journal
|
PGR (Progesterone receptor) • AR (Androgen receptor)
|
HR positive • AR positive • ER positive + PGR positive • PGR positive
over1year
Resistance to androgen receptor signaling inhibition does not necessitate development of neuroendocrine prostate cancer. (PubMed, JCI Insight)
Additionally, phenotypic response to CRISPR-Cas9-mediated AR knockout in AR-positive CRPC cells was evaluated. These analyses document that: 1) ARSi-resistant NEPC can develop without androgen deprivation treatment; 2) AR signaling in ARSi-resistant AR+/NE+ double positive "amphicrine" mCRPCs does not suppress NE differentiation; 3) lack of AR expression does not necessitate acquiring a NE phenotype despite concomitant mutations/deletions in PTEN and TP53, and loss of RB1, but can occur via emergence of an AR-/NE- double negative prostate cancer (DNPC); 4) despite DNPC cells having homogeneous genetic driver mutations, they are phenotypically heterogeneous, expressing basal lineage markers alone or in combination with luminal lineage markers; and 5) AR loss is associated with AR promoter hypermethylation in NEPCs but not in DNPCs.
Journal
|
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • RB1 (RB Transcriptional Corepressor 1) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • SOX2
|
TP53 mutation • PTEN mutation • AR positive • RB1 deletion • AR expression • RB1 overexpression
over1year
[VIRTUAL] Multiplex liquid biopsy for AR pathway activity in metastatic androgen receptor-positive triple negative breast cancer (AACR 2021)
We report here the longitudinal evaluation of this liquid biopsy as part of a phase I trial (NCT03090165) of the anti-androgen bicalutamide with selective CDK4/6 inhibitor ribociclib in metastatic AR-TNBC. Peripheral blood was collected (n=11) prior to treatment, after two cycles of treatment, and at progression and processed using the VERSA (Versatile Exclusion-based Rare Sample Analysis) microfluidic chip that integrates CTC capture and downstream analysis. This study demonstrates the feasibility of a longitudinal multiplex liquid biopsy as a pharmacodynamic biomarker of AR pathway activity in AR-TNBC, and suggests that AR pathway activity in CTCs may provide additional information to solid tumor biopsy AR expression in predicting sensitivity to anti-androgens. This work also demonstrates for the first time the detection of AR-V7 in CTCs in anti-androgen resistant AR-TNBC, suggesting that AR-V7 expression may be a mechanism of anti-androgen resistance in AR-TNBC as it is in advanced prostate cancer.
Liquid biopsy
|
AR (Androgen receptor)
|
AR positive • AR expression • AR-V7 expression • AR splice variant 7 • AR splice variant 7 expression
|
Kisqali (ribociclib) • bicalutamide
over1year
Enzalutamide and Paclitaxel Before Surgery in Treating Patients With Stage I-III Androgen Receptor-Positive Triple-Negative Breast Cancer (clinicaltrials.gov)
P2b, N=37, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Sep 2021 --> Jun 2023 | Trial primary completion date: Sep 2020 --> Jun 2022
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
AR positive
|
paclitaxel • enzalutamide capsule
over1year
Cervical malignant mixed mesonephric tumour: A case report with local recurrence after six-years and next-generation sequencing analysis with particular reference to the ataxia telangiectasia mutated gene. (PubMed, Exp Ther Med)
The clinical significance of the observed ATM variant in the case reported herein is unknown. The present findings need further verification, as the mutation in ATM may result in chemotherapy resistance or conversely, may be exploited for targeted therapies.
Clinical • Journal • Next-generation sequencing
|
ER (Estrogen receptor) • PGR (Progesterone receptor) • ATM (ATM serine/threonine kinase) • AR (Androgen receptor) • CCND1 (Cyclin D1) • WT1 (WT1 Transcription Factor) • CEACAM5 (CEA Cell Adhesion Molecule 5) • NKX2-1 (NK2 Homeobox 1) • MME (Membrane Metalloendopeptidase) • PAX8 (Paired box 8) • GATA3 (GATA binding protein 3)
|
AR positive • CDKN2A negative
over1year
Parotid Salivary Duct Carcinoma With a Prominent Squamous Component: Immunohistochemical Profile, Diagnostic Pitfalls, and Therapeutic Implications. (PubMed, Int J Surg Pathol)
Apart from the variable morphology, the typical salivary duct and squamous cell carcinoma tumor components also showed significant immunohistochemical differences, including differential staining of human epidermal growth factor receptor 2/neu. The associated diagnostic pitfalls, distinct immunoprofiles of the tumor components, helpful adjuncts for making the correct diagnosis, and associated therapeutic implications are discussed.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
|
AR positive
over1year
Activity of Seviteronel in Patients With Androgen Receptor (AR)-Positive Glioblastoma (clinicaltrials.gov)
P2a, N=4, Terminated, St Vincent's Hospital, Sydney | N=16 --> 4 | Trial completion date: Aug 2021 --> Feb 2021 | Recruiting --> Terminated | Trial primary completion date: Aug 2020 --> Feb 2021; Sponsor
Clinical • Enrollment change • Trial completion date • Trial termination • Trial primary completion date
|
AR (Androgen receptor)
|
AR positive
|
seviteronel (INO-464)
over1year
Androgen receptor expression and outcome of neoadjuvant chemotherapy in triple-negative breast cancer. (PubMed, Eur Rev Med Pharmacol Sci)
Our data seem to confirm that the LAR phenotype is associated to lower rates of pCR after neoadjuvant chemotherapy; routine assessment of AR expression in addition to classical biomarkers in patients with TNBC could help to better personalize treatment.
Clinical • Journal • BRCA Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor) • BRCA (Breast cancer early onset)
|
HER-2 overexpression • HER-2 expression • AR positive • AR expression
over1year
Identification of BXDC2 as a Key Downstream Effector of the Androgen Receptor in Modulating Cisplatin Sensitivity in Bladder Cancer. (PubMed, Cancers (Basel))
We identified BXDC2 as a key molecule in enhancing cisplatin sensitivity. AR-ERK activation may thus be associated with chemoresistance via downregulating BXDC2 expression in bladder cancer.
Journal
|
AR (Androgen receptor)
|
AR positive
|
cisplatin
over1year
Luteolin suppresses androgen receptor-positive triple-negative breast cancer cell proliferation and metastasis by epigenetic regulation of MMP9 expression via the AKT/mTOR signaling pathway. (PubMed, Phytomedicine)
Our findings indicate that luteolin inhibited the proliferation and metastasis of androgen receptor-positive TNBC by regulating MMP9 expression through a reduction in the levels of AKT/mTOR-inducing H3K27Ac and H3K56Ac.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • MMP9 (Matrix metallopeptidase 9)
|
AR positive • ER expression
over1year
Taselisib and Enzalutamide in Treating Patients With Androgen Receptor Positive Triple-Negative Metastatic Breast Cancer (clinicaltrials.gov)
P1/2, N=30, Active, not recruiting, Vanderbilt-Ingram Cancer Center | Trial completion date: Dec 2020 --> Dec 2021
Clinical • Trial completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HER-2 negative • AR positive • ER negative • PGR negative
|
enzalutamide capsule • taselisib (GDC-0032)
over1year
Abiraterone Acetate in Molecular Apocrine Breast Cancer (clinicaltrials.gov)
P2, N=34, Completed, UNICANCER | Active, not recruiting --> Completed
Clinical • Trial completion
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HER-2 negative • AR positive
|
abiraterone acetate • prednisone
over1year
Study on Androgen Receptor and Triple Negative Breast Cancer (clinicaltrials.gov)
P2, N=90, Recruiting, UNICANCER | Trial completion date: Sep 2021 --> Dec 2023 | Trial primary completion date: Mar 2020 --> Oct 2021
Clinical • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HER-2 negative • AR positive
|
capecitabine • Nubeqa (darolutamide)
over1year
The efficacy and safety of enzalutamide with trastuzumab in patients with HER2+ and androgen receptor-positive metastatic or locally advanced breast cancer. (PubMed, Breast Cancer Res Treat)
Enzalutamide plus trastuzumab was well tolerated, and a subset of patients in this heavily pretreated population had durable disease control. Determination of biomarkers is needed to identify patients most likely to benefit from this combination. CLINICALTRIALS.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
|
AR positive • EGFR positive • AR expression
|
Herceptin (trastuzumab) • enzalutamide capsule
over1year
[VIRTUAL] Biomarkers Expression in Triple Negative Breast Cancer (TNBC) (USCAP 2021)
By IHC three major clusters of TNBC based on p53, p16 and RB can be identified. AR is expressed across the major TNBC subtypes. PDL-1 is positive in significantly higher proportion of TNBC-NOS.
PD(L)-1 Biomarker • BRCA Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • AR (Androgen receptor) • RB1 (RB Transcriptional Corepressor 1) • BAP1 (BRCA1 Associated Protein 1) • MSH6 (MutS homolog 6) • MLH1 (MutL homolog 1) • MSH2 (MutS Homolog 2) • PMS2 (PMS1 protein homolog 2)
|
PD-L1 negative • AR positive
|
VENTANA PD-L1 (SP142) Assay
over1year
Clinicopathological characteristics and prognostic marker of triple-negative breast cancer in older women. (PubMed, Hum Pathol)
In multivariate analyses, AR positivity was an independent predictor of a favorable outcome in older patients (lower recurrence rate), whereas high-TILs was favorable in younger patients (lower recurrence and mortality rates). AR positivity or apocrine morphology was frequent and predicts a favorable clinical outcome in older TNBC patients, suggesting the importance of AR examination in this population.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • AR (Androgen receptor)
|
AR positive • TILs
over1year
Chromosome X aneusomy and androgen receptor gene copy number aberrations in apocrine carcinoma of the breast. (PubMed, Virchows Arch)
AR regulator genes, including the MAGE family, UXT and FLNA, presented variable methylation levels, but were mainly hypomethylated and therefore all transcriptionally active. The results of this study indicate that CADs present AR monosomy, paralleled by higher transcriptional activity of the gene with potential to influence response to AR deprivation therapy.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
over1year
Ablation of LGR4 signaling enhances radiation sensitivity of prostate cancer cells. (PubMed, Life Sci)
In all, our study suggested that LGR4 might serve as an important regulator of radiation sensitivity in PCa.
Journal
|
AR (Androgen receptor) • RSPO1 (R-Spondin 1)
|
AR positive • AR expression
|
enzalutamide capsule • R-Spondin1 (NU-206)
over1year
Salivary Duct Carcinoma: An Aggressive Salivary Gland Carcinoma with Morphologic Variants, Newly Identified Molecular Characteristics, and Emerging Treatment Modalities. (PubMed, Surg Pathol Clin)
For SDC, current treatment strategies are aggressive and commonly include surgical excision with lymph node dissection and adjuvant radiotherapy. Continued research is examining the utility of androgen deprivation therapy and targeted molecular therapy.
Review • Journal
|
ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
AR positive • ER negative • PGR negative
over1year
Ribociclib and Bicalutamide in AR+ TNBC (clinicaltrials.gov)
P1/2, N=37, Active, not recruiting, Ruth O'Regan, M.D. | N=11 --> 37
Clinical • Enrollment change • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
|
HER-2 negative • AR positive
|
Kisqali (ribociclib) • bicalutamide
over1year
Clinical • Enrollment change • Trial termination
|
AR (Androgen receptor)
|
AR positive
|
paclitaxel • docetaxel • capecitabine • bicalutamide
over1year
Androgen Receptor mRNA levels determine the prognosis in triple-negative breast cancer patients. (PubMed, BMC Cancer)
qRT-PCR was more sensitive and reliable in detecting the dynamic expression levels of AR compared to IHC and this variation could be explained by the higher sensitivity of the former method. High AR mRNA expression was strongly associated with expression of AR protein, high FOXA1/GATA3 mRNA, and with poor prognosis. qRT-PCR was more efficient in detecting the AR positive cases compared to IHC. A distinct signature involving high GATA3/FOXA1, low Ki67, and node positivity in AR mRNA positive tumors correlated with poor prognosis. Thus, AR mRNA screening can serve as an effective prognostic marker along with offering potential targeted therapy options for TNBC.
Clinical • Journal
|
AR (Androgen receptor) • FOXA1 (Forkhead Box A1)
|
AR positive • AR expression
over1year
A hemi-spleen injection model of liver metastasis for prostate cancer. (PubMed, Prostate)
The studies reported herein establish intrasplenic injection as a robust model of mCRPC liver metastasis. In addition, circulating PSA was validated as a noninvasive biomarker to longitudinally monitor overall tumor burden when using PSA+ models. Therefore, this model can be used to interrogate the pathophysiology of prostate cancer liver metastases, the microenvironmental factors permissive to such growth, immunologic variables, and the response of hepatic lesions to therapy.
Journal
|
HOXB13 (Homeobox B13)
|
AR positive
|
enzalutamide capsule • abiraterone acetate
over1year
Quadruple negative breast cancer. (PubMed, Breast Cancer)
However, QNBC has been shown to express unique proteins that may be amenable to use in the development of targeted therapies. Here we reviewed the features of QNBC and proteins that may serve as effective targets for QNBC treatment, such as ACSL4, SKP2, immune checkpoint inhibitors, EGFR, MicroRNA signatures and Engrailed 1.
Review • Journal • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
AR positive • ER expression
over1year
Male breast cancer: clinicopathological characterization of a National Danish cohort 1980-2009. (PubMed, Breast Cancer)
Male breast cancer is of luminal subtype, but more often Luminal B. Ki67 is crucial in evaluation of subtypes by immunohistochemistry, but have limitations. Subtyping seems to be of major importance. AR also can have a role in future treatment.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AR (Androgen receptor)
|
HER-2 negative • AR positive
over1year
Primary and Secondary/ Metastatic Salivary Duct Carcinoma Presenting within the Sinonasal Tract. (PubMed, Head Neck Pathol)
This small case series adds to the delineation of primary sinonasal SDC highlighting that almost half of invasive SDC presenting within sinonasal tract indeed represents extension or metastasis from a parotid gland primary. There is a tendency towards overrepresentation of HER2/neu-positive cases in both categories (primary and metastatic), but this needs clarification in larger studies.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
|
HER-2 amplification • AR positive
over1year
The combined effect of epigenetic inhibitors for LSD1 and BRD4 alters prostate cancer growth and invasion. (PubMed, Aging (Albany NY))
We investigated two different epigenetic modulating drugs, SP-2509 and JQ1, that target histone lysine demethylase 1 (LSD1), and bromodomain-containing protein (BRD), respectively and their combined effect in three different prostate cancer (PCa) types: 1) androgen receptor (AR)-positive and androgen-sensitive; 2) AR-positive but castration-resistant; and 3) androgen-nonresponsive. Our results suggest that these two epigenetic drugs are novel and promising compounds for the development of PCa therapeutics, particularly for castration-resistant disease. However, due to the potential risks, including metastasis, caution must be exercised in the clinical setting.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
|
JQ-1 • SP‐2509
over1year
Docosahexaenoic acid differentially modulates the cell cycle and metabolism- related genes in tumor and pre-malignant prostate cells. (PubMed, Biochim Biophys Acta Mol Cell Biol Lipids)
Expression of androgen-regulated and nuclear receptors genes showed that DHA affected them in a distinct pattern in each cell line, but most converged to metabolism regulation, response to hormones, lipids and stress. In conclusion, regardless of androgenic or PTEN background DHA exerted antiproliferative effect associated to cell cycle impairment, lipid deregulation and oxidative stress, but differentially regulated gene expression probably due to distinct molecular features of each pathologic stage.
Journal
|
PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1)
|
AR positive
over1year
Effects of α-adrenergic receptor antagonists on the development and progression of urothelial cancer. (PubMed, Am J Cancer Res)
Our in vitro studies thus indicate that both urothelial tumorigenesis and tumor growth are inhibited by silodosin, but not by tamsulosin or naftopidil. Clinical data further suggest that even pharmacological doses (e.g. 0.1 µM) of silodosin contribute to preventing bladder cancer progression.
Journal
|
PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor)
|
AR positive • CDKN1B expression
|
Zaichang (naftopidil) • tamsulosin
over1year
A new compound targets the AF-1 of androgen receptor and decreases its activity and protein levels in prostate cancer cells. (PubMed, Am J Cancer Res)
In xenograft mouse models, EIQPN blocked the tumor growth of androgen-independent prostate cancer cells. Overall, these findings indicate that EIQPN could serve as a novel therapeutic agent for advanced recurrent prostate cancers.
Journal
|
AR (Androgen receptor)
|
AR positive
over1year
Functional roles of antisense enhancer RNA for promoting prostate cancer progression. (PubMed, Theranostics)
The findings indicated that antisense eRNA was a functional RNA and may be a novel target that when suppressed improved prostate cancer therapy and diagnosis. New chromatin interaction among enhancer, promoter and gene-ending region might provide new insight into the spatiotemporal mechanism of the gene transcription and acting of bi-directional eRNAs.
Journal
|
AR (Androgen receptor) • DNMT1 (DNA methyltransferase 1)
|
AR positive
over1year
Androgen receptor expression inversely correlates with histological grade and N stage in ER/PgR male breast cancer. (PubMed, Breast Cancer Res Treat)
Hormonal factors reveal to play a crucial role in MBC carcinogenesis and progression. Intriguingly, in ER/PgR tumors AR expression significantly correlates with lymph node status, hinting at a favorable biological role of AR in this tumor subgroup.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
|
progesterone
over1year
Validation of Androgen Receptor loss as a risk factor for the development of brain metastases from ovarian cancers. (PubMed, J Ovarian Res)
We confirmed AR loss as predictive role for CNS involvement from EOC in an independent cohort of cases and controls. Early assessment of AR status could improve clinical management and patients' prognosis.
Clinical • Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
over1year
Clinical • Enrollment closed • Combination therapy
|
AR (Androgen receptor)
|
AR positive • AR expression
|
Erleada (apalutamide) • goserelin acetate
over1year
Journal
|
AR (Androgen receptor)
|
AR positive
over1year
Serial [F]-FDHT-PET to predict bicalutamide efficacy in patients with androgen receptor positive metastatic breast cancer. (PubMed, Eur J Cancer)
In this feasibility study, a bicalutamide-induced reduction in [F]-FDHT uptake could be detected by follow-up [F]-FDHT-PET in patients with AR + MBC. However, this change could not predict bicalutamide response.
Clinical • Journal
|
ER (Estrogen receptor) • AR (Androgen receptor)
|
AR positive
|
bicalutamide
over1year
Association Between the HER2 Protein Expression Level and the Efficacy of Neoadjuvant Chemotherapy in HER2-Positive Breast Cancer. (PubMed, Cancer Manag Res)
The present study included 296 patients with HER2-positive breast cancer receiving neoadjuvant chemotherapy (NAC) containing trastuzumab between January 2014 and November 2019...The HER2 protein expression level was related to multiple clinical features in patients with HER2-positive breast cancer. For example, hormone receptor, androgen receptor, cytokeratin5/6, and HER2 protein expression level may be used to predict the response to NAC in patients with HER2-positive breast cancer and may serve as a predictive factor for NAC efficacy.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
|
HER-2 positive • HER-2 expression • AR positive
|
Herceptin (trastuzumab)
over1year
The clinicopathological significance and prognostic value of programmed death-ligand 1 in prostate cancer: a meta-analysis of 3133 patients. (PubMed, Aging (Albany NY))
The study revealed that high expression of PD-L1 was related to unfavorable prognosis and advanced clinicopathological factors in PCa patients.
Retrospective data • Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • AR (Androgen receptor)
|
PD-L1 overexpression • AR positive
over1year
Pembrolizumab and Enobosarm in Treating Patients With Androgen Receptor Positive Metastatic Triple Negative Breast Cancer (clinicaltrials.gov)
P2, N=29, Active, not recruiting, City of Hope Medical Center | Trial completion date: Nov 2020 --> Nov 2021 | Trial primary completion date: Nov 2020 --> Nov 2021
Clinical • Trial completion date • Trial primary completion date • PD(L)-1 Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HER-2 negative • AR positive • ER expression
|
Keytruda (pembrolizumab) • Ostarine (enobosarm)
over1year
Androgen receptor modulates metastatic routes of VHL wild-type clear cell renal cell carcinoma in an oxygen-dependent manner. (PubMed, Oncogene)
The differential regulation of VEGF-A vs VEGF-C by AR may then result in differential impacts on the ccRCC metastatic destinations of VHL-wt ccRCC cells under different oxygen conditions. These finer mechanisms may help in the development of a novel therapy to better suppress the ccRCC progression under different oxygenization conditions.
Journal
|
AR (Androgen receptor) • VHL (von Hippel-Lindau tumor suppressor) • miR-185 (MicroRNA 185)
|
AR positive • VHL mutation • VEGFA expression
over1year
A Positive Feedback Loop Between TGFβ and Androgen Receptor Supports Triple-Negative Breast Cancer Anoikis Resistance. (PubMed, Endocrinology)
Finally, inhibiting both AR and TGFβ decreased cell survival, particularly under anchorage independent conditions. These findings warrant further investigations into whether combined inhibition of AR and TGFβ pathways might decrease metastatic recurrence rates and mortality from TNBC.
Journal
|
ER (Estrogen receptor) • AR (Androgen receptor) • TGFB1 (Transforming Growth Factor Beta 1)
|
AR positive • ER negative • AR expression
|
enzalutamide capsule • galunisertib (LY2157299)
over1year
Clinical • Trial completion • Enrollment change
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AR (Androgen receptor)
|
ER positive • HER-2 negative • AR positive
|
Ostarine (enobosarm)
over1year
Functional characterization of androgen receptor in two patient-derived xenograft models of triple negative breast cancer. (PubMed, J Steroid Biochem Mol Biol)
Considering that patient-derived xenografts (PDXs) are more appropriate than cell line-based models for recapitulating the structural and molecular features of a patient's tumor, we have identified and molecularly characterized two new AR-positive TNBC PDX models and assessed the impacts of AR agonist [dihydrotestosterone (DHT)] and antagonist (enzalutamide) on tumor growth and gene expression profiles by utilizing immunohistochemistry, western blots, and RNA-Seq analyses...Our results do not support that AR is a suitable therapeutic target in TNBC. To our best knowledge, the molecular mechanisms of AR in TNBC are equivocal and should be evaluated using clinically relevant models, considering both the heterogeneous expression of AR in TNBC and the general complexities of AR signaling.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
|
enzalutamide capsule
over1year
Quadruple-negative breast cancer: novel implications for a new disease. (PubMed, Breast Cancer Res)
Literature characterizing QNBC tumor biology and uncovering novel biomarkers for improved management of the disease remains scarce. In this comprehensive review, we summarize the current QNBC landscape and propose avenues for future research, suggesting potential biomarkers and therapeutic strategies that warrant investigation.
Review • Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
over1year
Ribociclib and Bicalutamide in AR+ TNBC (clinicaltrials.gov)
P1/2, N=11, Active, not recruiting, Ruth O'Regan, M.D. | Trial completion date: Sep 2021 --> Sep 2022 | Trial primary completion date: Sep 2020 --> Sep 2021
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
|
HER-2 negative • AR positive
|
Kisqali (ribociclib) • bicalutamide
over1year
AR facilitates YAP-TEAD interaction with the AM promoter to enhance mast cell infiltration into cutaneous neurofibroma. (PubMed, Sci Rep)
Consequently, the upregulated AM enhanced mast cell recruitment. Interruption of the YAP-TEAD interaction or inhibition of AM could impair mast cell accumulation induced by active AR, which indicated that this newly found signalling pathway may provide novel targets for cNF treatment.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
over1year
Pharmacological inhibition of androgen receptor expression induces cell death in prostate cancer cells. (PubMed, Cell Mol Life Sci)
Animal xenograft experiments showed that S-saponin treatment significantly reduced tumor growth of AR-positive 22Rv1 xenografts but not AR-negative PC-3 xenografts. Taken together, for the first time, our results revealed that S-saponin induces mitochondrial-mediated cell death in androgen-dependent and castration-resistant cells through regulation of AR mechanisms, including downregulation of Bcl-xL expression and induction of ROS stress by decreasing mitochondrial membrane potential.
Journal
|
AR (Androgen receptor) • BCL2L1 (BCL2-like 1) • TMPRSS2 (Transmembrane serine protease 2)
|
AR positive • AR overexpression • AR expression
over1year
Rosemary (Rosmarinus officinalis L.) extract inhibits prostate cancer cell proliferation and survival by targeting Akt and mTOR. (PubMed, Biomed Pharmacother)
In addition, treatment of the androgen-sensitive 22RV1 prostate cancer cells with RE resulted in a significant inhibition of proliferation and survival while RE had no effect on normal prostate epithelial PNT1A cells. These findings suggest that RE has potent effects against prostate cancer and warrants further investigation.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
over1year
[VIRTUAL] Molecular profiling of breast carcinoma in patients of African origin (ECP 2020)
Unexpectedly, Ki67 showed very low expression in Nigerian patients. Our data highlight differences in the immunohistochemical profile between the African and European breast cancer.
Clinical
|
AR (Androgen receptor) • GATA3 (GATA binding protein 3)
|
AR positive
over1year
[VIRTUAL] Molecular profiling of breast carcinoma in patients of African origin (ECP 2020)
Unexpectedly, Ki67 showed very low expression in Nigerian patients. Our data highlight differences in the immunohistochemical profile between the African and European breast cancer.
Clinical
|
AR (Androgen receptor) • GATA3 (GATA binding protein 3)
|
AR positive
over1year
[VIRTUAL] Molecular profiling of breast carcinoma in patients of African origin (ECP 2020)
Unexpectedly, Ki67 showed very low expression in Nigerian patients. Our data highlight differences in the immunohistochemical profile between the African and European breast cancer.
Clinical
|
AR (Androgen receptor) • GATA3 (GATA binding protein 3)
|
AR positive
almost2years
Alternative Splicing Regulation by the Androgen Receptor in Prostate Cancer Cells. (PubMed, J Steroid Biochem Mol Biol)
These genes encode metabolic enzymes such as the prostate-specific membrane antigen, encoded by FOLH1, and the malate dehydrogenase 1 (MDH1). Overall, our study presents a comprehensive analysis of the PCa cell transcriptome and its modulation by AR, revealing a significant enrichment of metabolic genes in this AR-dependent regulation of alternative splicing.
Journal
|
AR (Androgen receptor) • TSC2 (TSC complex subunit 2) • FOLH1 (Folate hydrolase 1) • CTBP1 (C-Terminal Binding Protein 1)
|
AR positive
almost2years
Journal
|
ER (Estrogen receptor) • AR (Androgen receptor) • ERCC1 (Excision repair cross-complementation group 1)
|
ER positive • AR positive • AR expression
almost2years
A Phase II Clinical Trial of Pembrolizumab and Enobosarm in Patients with Androgen Receptor-Positive Metastatic Triple-Negative Breast Cancer. (PubMed, Oncologist)
The combination of enobosarm and pembrolizumab was well tolerated with a modest clinical benefit rate of 25% at 16 weeks in heavily pretreated AR TNBC without pre-selected PD-L1. Future clinical trials combining AR targeted therapy with immune checkpoint inhibitor (ICI) for AR TNBC warrant investigation.
Clinical • P2 data • Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • AR (Androgen receptor)
|
AR positive • AR overexpression • AR expression
|
Keytruda (pembrolizumab) • Ostarine (enobosarm)
almost2years
High Ki-67 expression is a marker of poor survival in apocrine breast carcinoma. (PubMed, Pol J Pathol)
Favourable trend in OS was noted for patients with smaller tumours (p = 0.053), without lymph node metastases (p = 0.074) and without EGFR expression (p = 0.060). In apocrine breast carcinoma expression of Ki-67 is one of the most important factors influencing patients' survival.
Journal
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HER-2 expression • EGFR expression • AR positive • PGR positive • EGFR positive • MSLN positive
almost2years
Significance of glucocorticoid signaling in triple-negative breast cancer patients: a newly revealed interaction with androgen signaling. (PubMed, Breast Cancer Res Treat)
This is the first study to reveal that the interaction of GR and AR did influence the clinical outcome of TNBC patients and GCs induced cell migration in TNBC cells.
Clinical • Journal
|
AR (Androgen receptor)
|
AR positive
|
dexamethasone
almost2years
A serous borderline ovarian tumour in a transgender male adolescent. (PubMed, Br J Cancer)
To our knowledge, this is the second report of borderline tumour in a transgender individual and the first in an adolescent, an age group in which borderline tumours are extremely rare. We discuss the specific considerations of treating ovarian tumours in the transgender male population, the incompletely understood role of androgens in the genesis of ovarian epithelial neoplasia, and an emphasis on assessing cancer risk in transgender patients based on patient anatomy.
Journal
|
AR (Androgen receptor)
|
AR positive
almost2years
Clinical • Enrollment change
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HER-2 negative • AR positive • PGR negative
|
Ostarine (enobosarm)
almost2years
Androgen Receptor in Breast Cancer-Clinical and Preclinical Research Insights. (PubMed, Molecules)
However, since the prognostic and predictive value of AR positivity remains uncertain, it is difficult to identify and stratify patients that would benefit from AR-targeted therapies. Herein, through a review of preclinical studies, clinical studies, and clinical trials, we summarize the biology of AR, its prognostic and predictive value, as well as its therapeutic implications by breast cancer molecular subtype.
Review • Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
almost2years
[VIRTUAL] Novel Immunotherapy Combinations Against Castration-Resistant Prostate Cancer (PCF 2020)
Latest clinical study reported that an anti-PD-1 antibody Keytruda have antitumor activity in patients with metastatic castration resistant prostate cancer (CRPC) refractory to docetaxel. Furthermore, our preliminary results found that LLS30 was able to significantly prevent Gal-1 mediated T cell apoptosis in vitro and potentiate the anticancer effects of anti-PD-1 immunotherapy in Myc-CaP syngeneic mouse model. unding Acknowledgments: DOD PCRP W81XWH1910532
PD(L)-1 Biomarker • IO biomarker
|
AR (Androgen receptor)
|
AR positive
|
Keytruda (pembrolizumab) • docetaxel
almost2years
18F-fluorodeoxyglucose uptake on PET/computed tomography in association with androgen receptor expression and other clinicopathologic factors in surgically resected triple-negative breast cancer. (PubMed, Nucl Med Commun)
Androgen receptor-positive TNBC showed lower F-FDG uptake than androgen receptor-negative triple-TNBC. Tumor size, histological grade, Ki-67 and the presence of DCIS significantly influenced F-FDG uptake in TNBC.
Clinical • Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
almost2years
[VIRTUAL] Apocrine Ductal Carcinoma In Situ Associated With Testosterone Therapy in a Transgender Individual (CAP 2020)
We present a patient with negative screening mammography who developed apocrine DCIS on TT and draw attention to this entity within the transgender population because our findings may have implications for increased surveillance. This finding of DCIS warrants establishing culturally sensitive breast cancer screening protocols for transgender individuals.
Clinical
|
ER (Estrogen receptor) • AR (Androgen receptor)
|
AR positive • ER negative
almost2years
[VIRTUAL] Immunohistochemical Surrogates for Molecular Subtyping and Androgen Receptor and p53 Status in Triple-Negative Breast Cancers Are Useful Predictors of Prognosis (CAP 2020)
Our TNBC rates were comparable to the published rates of 10% to 17%. Nearly all (99%) were BLBCs. Aggressive clinical course, including death, and increased rates of germline mutations were noted.
BRCA Biomarker
|
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • AR (Androgen receptor)
|
TP53 mutation • AR positive
almost2years
Inhibition of EZH2 enhances the antitumor efficacy of metformin in prostate cancer. (PubMed, Mol Cancer Ther)
However, GSK126 can inhibit the methyltransferase-dependent interaction between AR and EZH2, thus restoring metformin's efficacy in androgen-refractory PCa cells. Collectively, our finding suggests that the combination of metformin and GSK126 would be an effective approach for future PCa therapy, and particularly effective for AR-positive CRPC.
Clinical • Journal
|
AR (Androgen receptor) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)
|
AR positive
|
metformin • GSK2816126
almost2years
CHD1 and SPOP synergistically protect prostate epithelial cells from DNA damage. (PubMed, Prostate)
Our results indicate that SPOP and CHD1 can synergistically promote repair of naturally occurring or chemically induced DNA damages in prostate epithelial cells. Regarding the progression of the SPOP/CHD1 subtype of PCa, other functionally complementary drivers warrant further identification. The clinical implication is that this subtype of PCa may be particularly sensitive to poly(ADP-ribose) polymerase inhibitors or DNA-damaging agents.
Journal
|
AR (Androgen receptor) • HRD (Homologous Recombination Deficiency) • RAD51 (RAD51 Homolog A)
|
AR positive
|
irinotecan
almost2years
[VIRTUAL] A phase 2 study evaluating orteronel, an inhibitor of androgen biosynthesis, in patients with androgen receptor (AR)-expressing metastatic triple-negative breast cancer (TNBC) (SABCS 2020)
Conclusions : Orteronel monotherapy was well tolerated but demonstrated limited clinical activity in this heavily pre-treated metastatic AR+ TNBC patient population. As novel AR targeting agents are being developed, future studies are needed to identify AR+ breast cancer patients most likely to benefit from AR inhibition.
Clinical • P2 data • IO biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor)
|
AR positive • AR overexpression • AR expression • PGR negative
|
orteronel (TAK 700)
almost2years
[VIRTUAL] Computational modeling of androgen receptor (AR) and estrogen receptor as predictive biomarkers of response to AR agonists and antagonists (SABCS 2020)
RAD140 and enzalutamide are compelling candidates for monotherapy or combination with anti-estrogen therapies in ER+/AR+ breast cancer. Future clinical validation of the models and therapeutic effect is warranted.
ER (Estrogen receptor) • AR (Androgen receptor)
|
AR positive • AR expression
|
enzalutamide capsule • vosilasarm (RAD140)
almost2years
[VIRTUAL] First efficacy results of a 2-stage Simon’s design randomised phase 2 of darolutamide or capecitabine in patients with triple-negative, androgen receptor positive advanced breast cancer (UCBG06-3) (SABCS 2020)
According to the planned interim analysis, the efficacy objective is met (5 CBR) in D arm. Moreover, darolutamide is well tolerated. Thus, patients are now recruited in the second stage.
Clinical • P2 data
|
AR (Androgen receptor)
|
AR positive • AR expression
|
capecitabine • Nubeqa (darolutamide)
almost2years
Clinicopathological Relevance and Prognostic Value of Androgen Receptor in Mammary Paget's Disease with Underlying Invasive Ductal Carcinoma. (PubMed, Oncol Res Treat)
In contrast to AR-negative tumors, patients with AR-positive ones were more likely to have lower BMI, no ALN metastasis, and better OS. AR-targeted treatments for MPD-IDC may add to existing therapeutic approaches to improve their effectiveness.
Clinical • Retrospective data • Journal
|
ER (Estrogen receptor) • AR (Androgen receptor)
|
AR positive • AR expression
almost2years
Androgen receptor expression in a Sri Lankan patient cohort with early breast carcinoma. (PubMed, BMC Womens Health)
AR prevalence obtained was low. AR positivity was associated with positivity for ER and PR. On multivariate analysis, apart from TNM stage only ER/AR status were predictive of OS and DFS, with concordant expression of ER/AR demonstrating a better, early survival.
Clinical • Journal
|
ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
ER positive • AR positive • AR expression
almost2years
A highly potent PROTAC androgen receptor (AR) degrader ARD-61 effectively inhibits AR-positive breast cancer cell growth in vitro and tumor growth in vivo. (PubMed, Neoplasia)
ARD-61 effectively induces complete AR degradation in xenograft tumor tissue and is more effective than enzalutamide in achieving tumor growth inhibition in the MDA-MB-453 xenograft model in mice. Our study provides strong preclinical rationale to develop AR degraders for the treatment of AR+ human breast cancer.
Preclinical • Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
|
enzalutamide capsule
almost2years
Iron induces cell death and strengthens the efficacy of anti-androgen therapy in prostate cancer models. (PubMed, Clin Cancer Res)
Our models allow us to dissect the direct iron effect on cancer cells. We demonstrate the proof of principle that iron toxicity inhibits PCa cell proliferation, proposing a novel tool to strengthen anti-androgen treatment efficacy.
Clinical • Preclinical • Journal
|
AR (Androgen receptor)
|
AR positive
|
bicalutamide
almost2years
Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer. (PubMed, Int J Mol Sci)
Then, considering the need to confirm by experimental approaches the correlations suggested by the bioinformatics analyses, we decided to evaluate the gene expression levels of the twenty-five selenoproteins and six HUB nodes in androgen receptor-positive (22RV1 and LNCaP) and androgen receptor-negative (DU145 and PC3) cell lines, compared to human nontransformed, and differentiated, prostate epithelial cells (EPN) by RT-qPCR analysis. This analysis confirmed that the combined evaluation of some selenoproteins and HUB nodes could have prognostic value and may improve patient outcome predictions.
Journal
|
AR (Androgen receptor)
|
AR positive
almost2years
Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer. (PubMed, Nat Commun)
Genetic and chemical inhibition of DOT1L selectively impaired the viability of androgen receptor (AR)-positive PCa cells and organoids, including castration-resistant and enzalutamide-resistant cells...This leads to further repression of MYC in a negative feed forward manner. Thus DOT1L selectively regulates the tumorigenicity of AR-positive prostate cancer cells and is a promising therapeutic target for PCa.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AR (Androgen receptor)
|
AR positive • MYC expression • MLL fusion
|
enzalutamide capsule
almost2years
Journal
|
AR (Androgen receptor)
|
AR positive
|
enzalutamide capsule
almost2years
Circular RNA cir-ITCH Is a Potential Therapeutic Target for the Treatment of Castration-Resistant Prostate Cancer. (PubMed, Biomed Res Int)
Taken together, these data demonstrated that cir-ITCH plays a tumor-suppressive role in human PCa cells, partly through the Wnt/β-catenin and PI3K/AKT/mTOR pathways. Thus, cir-ITCH may serve as a novel therapeutic target for the treatment of PCa, especially castration-resistant prostate cancer.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
almost2years
Journal
|
PTEN (Phosphatase and tensin homolog) • AR (Androgen receptor) • ERG (ETS Transcription Factor ERG) • TMPRSS2 (Transmembrane serine protease 2)
|
ER positive • PTEN deletion • AR positive • AR expression • TMPRSS2-ERG fusion
almost2years
The dual androgen receptor and glucocorticoid receptor antagonist CB-03-10 as potential treatment for tumors that have acquired GR-mediated resistance to AR blockade. (PubMed, Mol Cancer Ther)
Importantly, these compounds lack biologically relevant AR/GR agonist activities. Overall, these preclinical findings support the selection of CB-03-10 for further development as an anticancer agent in cases where resistance to AR-targeted therapy or chemotherapy, via upregulation of GR activity, continues to limit the efficacy and duration of clinical benefit with these interventions.
Journal
|
AR (Androgen receptor)
|
AR positive
|
Winlevi (clascoterone cream 1%)
almost2years
Exosomes-Mediated Transfer of Itga2 Promotes Migration and Invasion of Prostate Cancer Cells by Inducing Epithelial-Mesenchymal Transition. (PubMed, Cancers (Basel))
Our findings indicate the possible role of the exosomal-ITGA2 transfer in altering the phenotype of AR-positive cells towards more aggressive phenotype. Thus, interfering with exosomal cargo transfer may inhibit the development of aggressive phenotype in PCa cells.
Journal
|
AR (Androgen receptor)
|
AR positive
almost2years
Anticancer Imidazoacridinone C-1311 is Effective in Androgen-Dependent and Androgen-Independent Prostate Cancer Cells. (PubMed, Biomedicines)
In contrast, in AR-independent PCa cells, C-1311 targeted the cellular metabolism and inhibited the genes regulating glycolysis and gluconeogenesis. Together, these results indicate that C-1311 warrants further development for the treatment of PCa.
Journal
|
AR (Androgen receptor) • KLK3 (Kallikrein-related peptidase 3)
|
AR positive
almost2years
YATAGARASU: A Study of Apalutamide Combined With GnRH Agonist in Participants With Androgen Receptor Positive Salivary Gland Carcinoma (clinicaltrials.gov)
P2, N=24, Recruiting, Janssen Pharmaceutical K.K. | Trial completion date: Sep 2022 --> Jul 2021 | Trial primary completion date: Nov 2021 --> Mar 2021
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
AR (Androgen receptor)
|
AR positive • AR expression
|
Erleada (apalutamide) • goserelin acetate
almost2years
Differentiation of Basal Cell Carcinoma and Trichoepithelioma: An Immunohistochemical Study. (PubMed, Am J Dermatopathol)
Similarly, the sensitivity for borderline/equivocal BCC was 55.6%, whereas the specificity was 100%. Although moderately sensitive, combining both immunomarkers showed an excellent specificity to discriminate between BCC and TE.
Journal
|
BCL2 (B-cell CLL/lymphoma 2) • AR (Androgen receptor)
|
AR positive
almost2years
Expression of the of the androgen receptor governs radiation resistance in a subset of glioblastomas vulnerable to anti-androgen therapy. (PubMed, Mol Cancer Ther)
Antiandrogens blocked the ability of AR-positive GBM patient-derived xenografts to engage adaptive transcriptional programs following radiation and slowed the repair of radiation-induced DNA damage. These results suggest that combining blood-brain barrier permeable antiandrogens with radiation may have promise for patients with AR-positive GBMs.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
almost2years
Androgen receptor reverses the oncometabolite R-2-hydroxyglutarate-induced prostate cancer cell invasion via suppressing the circRNA-51217/miRNA-646/TGFβ1/p-Smad2/3 signaling. (PubMed, Cancer Lett)
Preclinical studies with an in vivo xenograft mouse model also revealed that PCa cells with the IDH1 R132H mutation have more invasive metastasis. This study demonstrates that IDH1 R132H mutation with increased oncometabolite R-2HG in PCa cells may play important roles to increase PCa cell invasion.
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • AR (Androgen receptor)
|
IDH1 mutation • AR positive • IDH1 R132H
almost2years
Androgen receptor expression is useful to predict the therapeutic effect in HER2-positive breast carcinoma. (PubMed, Breast Cancer Res Treat)
High AR expression may be a useful predictor of therapeutic effects and prognosis in both subgroups of HER2 + BCs.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HER-2 positive • HR positive • HER-2 expression • AR positive • AR expression • HR positive + HER-2 positive
2years
Androgen Receptor Expression and Its Correlation with Clinicopathological Parameters in Iranian Patients with Triple Negative Breast Cancer. (PubMed, Iran J Pathol)
Low percentage of TNBC patients expressed AR and no significant correlation was observed between its expression and most of the clinicopathological parameters. AR may not be a suitable biomarker and treatment target for the Iranian patients with TNBC.
Clinical • Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
2years
Journal
|
AR (Androgen receptor)
|
AR positive
2years
Expression of androgen receptor in primary breast carcinoma and its relation with clinicopathologic features, estrogen, progesterone, and her-2 receptor status. (PubMed, J Cancer Res Ther)
Indian patients with breast carcinoma have a higher AR expression in low-grade and ER/PR-positive tumors, in concordance with Western studies. A good number of triple-negative tumors also express AR, which needs further evaluation.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
HER-2 positive • HER-2 expression • AR positive • AR expression
2years
The β2-adrenergic receptor is a molecular switch for neuroendocrine transdifferentiation of prostate cancer cells. (PubMed, Mol Cancer Res)
In conclusion, high ADRB2 expression is required for ADT-induced NEtD, characterized by ADRB2 downregulation and t-NEPC emergence. Implications: This data suggest a potential application of β-blockers to prevent cancer cells committed to a neuroendocrine lineage from evolving into t-NEPC.
Journal
|
AR (Androgen receptor)
|
AR positive
2years
The clinicopathological significance of the adipophilin and fatty acid synthase expression in salivary duct carcinoma. (PubMed, Virchows Arch)
ADP was associated with an aggressive histopathology and unfavorable prognosis, and FASN may biologically interact with the AR signaling pathway in SDC. ADP may, therefore, be a new prognostic indicator and therapeutic target in SDC.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor) • FOXA1 (Forkhead Box A1) • FASN (Fatty acid synthase) • PLIN2 (Perilipin)
|
HER-2 positive • AR positive • AR overexpression • AR expression • PLIN2 expression
2years
The Role of the Androgen Receptor in Prostate Cancer-induced Platelet Aggregation and Platelet-induced Invasion. (PubMed, J Thromb Haemost)
Androgen receptor loss within prostate cancer results in increased thrombogenicity due to upregulation of prothrombin expression. Reciprocally, platelets enhance invasion of androgen receptor-negative prostate cancer cells via increased MMP expression.
Journal
|
AR (Androgen receptor) • MMP2 (Matrix metallopeptidase 2)
|
AR positive • AR expression
|
dabigatran etexilate
2years
Phase II Study of Dehydroepiandrosterone in Androgen Receptor-Positive Metastatic Breast Cancer. (PubMed, Oncologist)
DHEA showed excellent safety but poor activity in MBC. Although dose and patient selection could be improved, high serum level variability may hamper further DHEA development in this setting.
P2 data • Journal
|
ER (Estrogen receptor) • AR (Androgen receptor)
|
ER positive • AR positive • AR expression • AR amplification
2years
Gene therapy for castration-resistant prostate cancer cells using JC polyomavirus-like particles packaged with a PSA promoter driven-suicide gene. (PubMed, Cancer Gene Ther)
In this study, we found that PSAtk-VLPs could only kill AR-positive CRPC 22Rv1 cells in vitro and inhibit the growth of tumor nodules in the xenograft mouse model. Our results reveal that PSAtk-VLPs could potentially be used as a new option for treating CRPC patients in the future.
Journal
|
AR (Androgen receptor) • KLK3 (Kallikrein-related peptidase 3)
|
AR positive
2years
Tumor-Infiltrating Lymphocyte • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • AR (Androgen receptor) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8)
|
AR positive
|
VENTANA PD-L1 (SP142) Assay
2years
Estrogen receptor β exerts tumor suppressive effects in prostate cancer through repression of androgen receptor activity. (PubMed, PLoS One)
In agreement with this, we find that the phosphorylation of the CAMKK2 target, AMPK, was repressed by ligand-activated ERβ. These findings suggest that ERβ-mediated signaling pathways are involved in the negative regulation of AR expression and activity, thus supporting a tumor suppressive role for ERβ in PCa.
Journal
|
ER (Estrogen receptor) • AR (Androgen receptor) • AMPK (Protein Kinase AMP-Activated Catalytic Subunit Alpha 1) • FKBP5 (FKBP Prolyl Isomerase 5)
|
AR positive • AR expression
2years
Androgen excess in breast cancer development: implications for prevention and treatment. (PubMed, Endocr Relat Cancer)
The key role of androgen excess in the genesis of different subtypes of breast cancer has significant clinical implications for both treatment and prevention. Our belief stems from a thorough analysis of the literature, where an abundance of evidence is present to justify a clinical trial that would investigate the effectiveness of treating the underlying excessive androgen production.
Review • Journal
|
AR (Androgen receptor)
|
ER positive • AR positive
2years
The Clinical Importance of Androgen Receptor Status in Response to Neoadjuvant Chemotherapy in Turkish Patients with Local and Locally Advanced Breast Cancer. (PubMed, Oncol Res Treat)
Our results show that AR positivity is associated with poor response to NACT in Turkish breast cancer patients and that AR positivity is independent of stage, hormone receptor status, HER-2 status, and disease stage.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
AR positive • AR expression
2years
ELL2 Is Required for the Growth and Survival of AR-Negative Prostate Cancer Cells. (PubMed, Cancer Manag Res)
Furthermore, knockdown of ELL2 caused S-phase cell cycle arrest, inhibition of CDK2 phosphorylation and cyclin D1 expression, and increased expression of cyclin E. ELL2 knockdown in PC-3 and DU145 cells induced S-phase cell cycle arrest and profound apoptosis, which was accompanied by the induction of genes associated with cell death and survival pathways. These observations suggest that ELL2 is a potential oncogenic protein required for survival and proliferation in AR-negative prostate cancer cells.
Journal
|
AR (Androgen receptor) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • CDK2 (Cyclin-dependent kinase 2) • IRF1 (Interferon Regulatory Factor 1)
|
AR positive • CCND1 expression • IRF1 expression
2years
Combination Chemohormonal Therapy in Metastatic Salivary Duct Carcinoma. (PubMed, Am J Case Rep)
Combination chemohormonal therapy (CHT) was initiated with carboplatin area under the curve 4 and paclitaxel, 200 mg/m² in 21-day cycles along with combined androgen blockade using leuprolide, 45 mg subcutaneously every 6 months and bicalutamide, 50 mg daily. CONCLUSIONS Combination CHT with carboplatin, paclitaxel, and combined androgen deprivation may be a good treatment option in androgen receptor-positive recurrent or metastatic SDC if rapid treatment response is desired. Combination chemotherapy with androgen deprivation for validation through clinical trials.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
|
HER-2 amplification • AR positive
|
carboplatin • paclitaxel • bicalutamide
2years
Prognostic role of androgen receptor expression in patients with metastatic triple negative breast cancer. (PubMed, Exp Oncol)
Five-year survival since diagnosis in the group with AR-positive TNBC was 47.6 ± 8.3% vs 20.0 ± 5.3% in the group with AR-negative TNBC (p < 0.05). The results of our study indicate a favorable impact of AR expression on the overall survival of TNBC patients.
Clinical • Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
2years
Discovery of Highly Potent and Efficient PROTAC Degraders of Androgen Receptor (AR) by Employing Weak Binding Affinity VHL E3 Ligase Ligands. (PubMed, J Med Chem)
ARD-266 is capable of reducing the AR protein level by >95% in these AR+ prostate cancer cell lines and effectively reduces AR-regulated gene expression suppression. For the first time, we demonstrated that an E3 ligand with micromolar binding affinity to its E3 ligase complex can be successfully employed for the design of highly potent and efficient PROTAC degraders and this finding may have a significant implication for the field of PROTAC research.
Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
2years
High Frequency of Triple Negative Breast Cancers Co-express p16 and SOX10 But Do Not Express AR. (PubMed, Hum Pathol)
In conclusion, p16 and SOX10 are frequently expressed in TNBC, regardless of CK5/6 expression. Furthermore, p16 and SOX10 are often co-expressed in TNBC compared to non-TNBCs.
Journal
|
AR (Androgen receptor) • SOX10 (SRY-Box 10)
|
AR positive
2years
Characterization of CD44 intracellular domain interaction with RUNX2 in PC3 human prostate cancer cells. (PubMed, Cell Commun Signal)
We have shown here a strong functional relationship between CD44-ICD and RUNX2 in PC3 cells. RUNX2 forms a complex with CD44-ICD as a co-transcriptional factor, and this complex formation not only activates the expression of metastasis-related genes but also contributes to migration and tumorsphere formation. Therefore, RUNX2 and CD44-ICD are potential targets for anti-cancer therapy, and attenuation of their interaction may validate the regulatory effects of these proteins on cancer migration and progression.
Journal
|
AR (Androgen receptor) • CD44 • SPP1 (Secreted Phosphoprotein 1) • MMP9 (Matrix metallopeptidase 9)
|
AR positive
2years
Androgen receptor immunohistochemistry in salivary duct carcinoma: a retrospective study of 188 cases focusing on Tumoral heterogeneity and temporal concordance. (PubMed, Hum Pathol)
A small subset may show intratumoral AR heterogeneity and discordant AR expression in metastasis. AR immunoexpression may be seen in non-SDC salivary gland carcinomas but it is uncommon and usually focal.
Retrospective data • Journal
|
AR (Androgen receptor)
|
AR positive • AR expression
2years
Bag-1L: a promising therapeutic target for androgen receptor-dependent prostate cancer. (PubMed, J Mol Endocrinol)
An alternative approach is to target key molecules such as the co-chaperone Bag-1L that bind to and enhance the activity of the AR AF-1. Here, we review recent literature that suggest Bag-1L is a promising target for AR positive prostate cancer.
Review • Journal
|
AR (Androgen receptor)
|
AR positive
2years
Mithramycin suppresses DNA damage repair via targeting androgen receptor in prostate cancer. (PubMed, Cancer Lett)
We show that MTM significantly impairs DDR and enhances the effectiveness of ionizing radiation or the radiomimetic agent Bleomycin in PCa. Thus, the combination of MTM treatment with RT or radiomimetic agents, such as bleomycin, may present a novel effective therapeutic strategy for patients with high-risk, clinically localized PCa.
Journal
|
AR (Androgen receptor)
|
AR positive • AR mutation
|
bleomycin
2years
Co-Expression of Androgen Receptor and Cathepsin D Defines a Triple-Negative Breast Cancer Subgroup with Poorer Overall Survival. (PubMed, Cancers (Basel))
AR/Cath-D co-expression independently predicted overall survival. Patients with TNBC in which AR and Cath-D are co-expressed could be eligible for combinatory therapy with androgen antagonists and anti-Cath-D human antibodies.
Clinical • Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • AR (Androgen receptor)
|
AR positive • AR expression • ER expression
2years
[VIRTUAL] The novel role of SPOP in regulating topoisomerase 2A in prostate cancer cells as a potential therapeutic marker for DNA repair targeted therapy (AUA 2020)
Our results suggest that SPOP is involved in the DNA-protein crosslink repair process through the elimination of TOP2A from the TOP2A cleavage complex in prostate cancer cell lines. These results imply that TOP inhibitor might be effective to AR-positive, SPOP-wild type prostate cancer. Also, PARP inhibitor might be effective to SPOP-mutated prostate cancer.
PARP Biomarker
|
AR (Androgen receptor) • TOP2A (DNA topoisomerase 2-alpha) • MRE11A (MRE11 homolog, double strand break repair nuclease)
|
AR positive
2years
[VIRTUAL] Androgen Deprivation Therapy Through the Peri-radiation Period Reduces the Risk of Bladder Hemorrhage in Prostate Cancer Patients Undergoing External Beam Radiotherapy (AUA 2020)
ADT through the peri-radiotherapy period has a potential for preventing radiation cystitis in patients with prostate cancer. Our results suggest that AR activation contributes to inducing angiogenesis in urothelial cells. Source of Funding: None
Clinical
|
AR (Androgen receptor) • KDR (Kinase insert domain receptor) • FLT1 (Fms-related tyrosine kinase 1)
|
AR positive
2years
Molecular Subtyping of Triple-Negative Breast Cancers by Immunohistochemistry: Molecular Basis and Clinical Relevance. (PubMed, Oncologist)
We developed an immunohistochemistry (IHC)-based classification approach for triple-negative breast cancer (TNBC), which exhibited substantial agreement with the mRNA expression-based classification. The implications for practice are as follows. Our IHC-based classification (a) allows for subgrouping of TNBC patients in large clinical trials and evaluating the efficacy of targeted therapies within certain subtypes, (b) will contribute to the practical application of subtype-specific treatment for patients with TNBC, and (c) can provide additional information beyond traditional prognostic factors in relapse prediction.
Clinical • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor) • CD8 (cluster of differentiation 8) • VEGFA (Vascular endothelial growth factor A)
|
AR positive
2years
[VIRTUAL] Androgen receptor expression and subcellular localization on circulating tumor cells in a Phase I trial of anti-androgen bicalutamide with CDK4/6 inhibitor ribociclib in metastatic androgen receptor-positive triple negative breast cancer (AACR-II 2020)
Baseline and longitudinal AR expression in patient CTCs was heterogeneous and will be correlated with clinical outcomes. In summary, we demonstrate the feasibility of prospective longitudinal assessment of AR expression and localization on CTCs in patients with AR+ TNBC receiving anti-androgen therapy, with ongoing work exploring the potential role of this as a predictive biomarker of anti-androgen sensitivity/response in AR+ TNBC.
P1 data • Circulating Tumor Cells
|
AR (Androgen receptor)
|
AR positive • AR expression
|
Kisqali (ribociclib) • bicalutamide
2years
[VIRTUAL] FT-6876, a potent and selective inhibitor of CBP/p300 with antitumor activity in AR-positive breast cancer (AACR-II 2020)
This was associated with a reduction in H3K27Ac, AR and ER target gene modulation, and reduction in Ki67. FT-6876 is a promising new CBP/p300 bromodomain inhibitor demonstrating efficacy in preclinical models of AR+ breast cancer.
PARP Biomarker • IO biomarker
|
ER (Estrogen receptor) • AR (Androgen receptor)
|
AR positive • AR expression
|
FT-6876
2years
[VIRTUAL] Visualizing bicalutamide effect on androgen receptor availability in patients with metastatic breast cancer (AACR-II 2020)
In this feasibility study, bicalutamide induced 18F-FDHT uptake change could be detected by repeated 18F-FDHT-PET in patients with AR positive metastatic breast cancer. However, in this small study, this change was not significantly related to bicalutamide response per patient. (NCT02697032)Funding by UMCG Healthy Ageing Pilots and de Cock-Hadders Foundation
Clinical
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AR (Androgen receptor)
|
AR positive • AR overexpression
|
bicalutamide
2years
Prognostic Role of Androgen Receptor Expression in Surgically Resected Early Breast Cancer Patients. (PubMed, J Breast Cancer)
We propose a cut-off value of 35% to best predict RFS in patients with surgically resected breast cancer. AR expression was positive in 68.4% of patients, and AR positivity was found to be an independent prognostic factor for longer RFS.
Clinical • Journal
|
AR (Androgen receptor)
|
EGFR expression • AR positive • EGFR positive • AR expression
over2years
Androgen receptor-positive triple negative breast cancer: From biology to therapy (PubMed, Bull Cancer)
Three clinical trials reported efficacy data for anti-androgens (bicalutamide, abiraterone acetate and enzalutamide) based on strong preclinical rationale. These encouraging but still limited results make a case for the identification of predictive response factors and therapeutic combinations to improve response rates. This review will provide an update on the biological and clinical knowledge of this tumoral subgroup that opens the way to non-cytotoxic anti-androgen therapies.
Review • Journal
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • AR (Androgen receptor)
|
PIK3CA mutation • AR positive • AR expression
|
enzalutamide capsule • abiraterone acetate • bicalutamide
over2years
Consideration of breast cancer subtype in targeting the androgen receptor. (PubMed, Pharmacol Ther)
Our analysis shows that a higher AR mRNA level is associated with improved disease outcome in patients with ER-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors, but with worse disease outcome in HER2-positive subgroups. In conclusion, next to AR expression, incorporation of additional tumor characteristics will potentially make AR targeting a more valuable therapeutic strategy in breast cancer.
Review • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • AR (Androgen receptor)
|
HER-2 positive • ER positive • HER-2 negative • EGFR expression • AR positive • EGFR positive • AR expression
over2years
[VIRTUAL] Metabolomic profiling to evaluate the pharmacodynamic of proxalutamide, a novel androgen receptor antagonist (EAU-I 2020)
LC-Q/TOF-MS was then used for analyzing intracellular metabolites in the four PCa cells before or after administration of proxalutamide and two other AR antagonists (bicalutamide and enzalutamide). Proxalutamide influenced the glutamate metabolism, redox homeostasis and pyrimidine synthesis in PCa cells, and these changes on metabolic and redox status in PCa cells may be associated with the blockade of AR signaling pathways.
PK/PD data
|
AR (Androgen receptor)
|
AR positive
|
enzalutamide capsule • bicalutamide • proxalutamide (GT0918)
over2years
[VIRTUAL] Biological and clinical features of early triple-negative invasive lobular carcinomas of the breast. (ASCO 2020)
All the c-erbB2 mutations found were previously reported to be pathogenetic in BCs and to predict response to neratinib... TN ILCs are rare tumors with dire prognosis. Their specific biological features require newly defined targeted therapeutic strategies. Research Funding: None
Clinical
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
|
HER-2 negative • AR positive • AR expression
|
Nerlynx (neratinib)
over2years
[VIRTUAL] Comprehensive profiling of androgen receptor-positive (AR+) triple-negative breast cancer (TNBC) patients (pts) treated with standard neoadjuvant therapy (NAT) +/- enzalutamide. (ASCO 2020)
Pts received 4 cycles of doxorubicin-based NAT (AC)...Immunohistochemistry (IHC) of AR+≥10% was the threshold for selecting ZT (enzalutamide 160 or 120 mg PO qD + paclitaxel 80 mg/m2 qW for 12 cycles)... The LAR TNBC subtype has a low pCR rate to NAT. Among pts with AC-insensitive TNBC, baseline upregulated androgen response pathway and LAR subtype may benefit from the ZT regimen, potentially by PI3K targeting. Research Funding: Pfizer, MD Anderson Cancer Center
Clinical
|
AR (Androgen receptor)
|
AR positive
|
paclitaxel • doxorubicin hydrochloride • enzalutamide capsule
over2years
[VIRTUAL] Translational relevance of androgen receptor immunohistochemistry scoring systems for data harmonization in triple negative breast cancer (TNBC). (ASCO 2020)
AR immunohistochemistry cut-offs using the Allred (≥3) and H-Score (≥30) are close to the ones used for ER/PR immunohistochemistry as per ASCO/CAP guidelines, making a strong case for universal application of these systems for harmonization of AR data. Research Funding: Astellas Pharma India Pvt. Ltd.
AR (Androgen receptor)
|
AR positive
over2years
Phase 2 Study of Seviteronel (INO-464) in Patients With Metastatic Castration-Resistant Prostate Cancer After Enzalutamide Treatment. (PubMed, Clin Genitourin Cancer)
Seviteronel was not generally well tolerated nor associated with significant clinical responses in patients with mCRPC who had previously received enzalutamide. Further investigation of single-agent seviteronel in this patient population is not warranted; however, studies investigating seviteronel with low-dose dexamethasone are ongoing in patients with androgen receptor-positive tumors.
Clinical • P2 data • Journal
|
AR (Androgen receptor) • CYP17A1 (Cytochrome P450 Family 17 Subfamily A Member 1) • KLK3 (Kallikrein-related peptidase 3)
|
AR positive
|
docetaxel • enzalutamide capsule • dexamethasone • Decadron (dexamethasone) • seviteronel (INO-464)
over2years
[VIRTUAL] Phase II study of enzalutamide in androgen receptor positive (AR+) recurrent high-grade and low-grade serous ovarian cancer (SGO-I 2020)
The study met its primary endpoint, with 13 patients (22%) remaining progression free at 6 months. However, the response rate was low. Enzalutamide was well tolerated and may offer a well-tolerated treatment option in select patients.
P2 data
|
AR (Androgen receptor)
|
AR positive
|
enzalutamide capsule
over2years
Y08197 is a novel and selective CBP/EP300 bromodomain inhibitor for the treatment of prostate cancer. (PubMed, Acta Pharmacol Sin)
Furthermore, treatment with Y08197 (5 μM) significantly decreased ERG-induced invasive capacity of 22Rv1 prostate cancer cells detected in wound-healing assay and cell migration assay. Taken together, CBP/EP300 inhibitor Y08197 represents a promising lead compound for development as new therapeutics for the treatment of castration-resistant prostate cancer.
Journal
|
MYC (V-myc avian myelocytomatosis viral oncogene homolog) • AR (Androgen receptor) • EP300 (E1A binding protein p300) • TMPRSS2 (Transmembrane serine protease 2)
|
AR positive • AR expression
over2years
MIIP inhibits the growth of prostate cancer via interaction with PP1α and negative modulation of AKT signaling. (PubMed, Cell Commun Signal)
We discovered that MIIP is a novel suppressor of oncogenic AKT-mTOR signaling in PCa by facilitating PP1-meditaed AKT dephosphorylation. Our study further emphasized the tumor suppressive role of MIIP and illustrated a novel mechanism.
Journal
|
AR (Androgen receptor) • mTOR (Mechanistic target of rapamycin kinase)
|
AR positive
over2years
Clinical significance of serum PSA in breast cancer patients. (PubMed, BMC Cancer)
Our data suggest that sPSA may reflect tumor biological properties including AR activity in post-menopausal breast cancer.
Clinical • Journal
|
AR (Androgen receptor) • KLK3 (Kallikrein-related peptidase 3)
|
AR positive
over2years
A comparative study of peptide-based imaging agents [Ga]Ga-PSMA-11, [Ga]Ga-AMBA, [Ga]Ga-NODAGA-RGD and [Ga]Ga-DOTA-NT-20.3 in preclinical prostate tumour models. (PubMed, Nucl Med Biol)
PET imaging using [Ga]Ga-AMBA and [Ga]Ga-DOTA-NT-20.3 demonstrates that GRPr and NTSR1 could represent viable alternative targets for diagnostic or therapeutic applications in PCa with limited PSMA expression levels. More preclinical and clinical studies will follow to explore this potential.
Preclinical • Journal
|
AR (Androgen receptor) • FOLH1 (Folate hydrolase 1) • KLK3 (Kallikrein-related peptidase 3)
|
AR positive
over2years
[VIRTUAL] Metabolomic profiling to evaluate the pharmacodynamic of Proxalutamide, a novel androgen receptor antagonist (AUA 2020)
LC-Q/TOF-MS was then used for analyzing intracellular metabolites in the four PCa cells before or after administration of proxalutamide and two other AR antagonists (bicalutamide and enzalutamide). Proxalutamide influenced the glutamate metabolism, redox homeostasis and pyrimidine synthesis in PCa cells (Fig.1c and 1d), and these changes may be associated with the blockade of AR signaling pathways. Source of Funding: Supported by National Nature Science Foundation of China (81703608) and Nanjing Medical Science and Technique Development Foundation(QRX17049)
PK/PD data
|
AR (Androgen receptor)
|
AR positive
|
enzalutamide capsule • bicalutamide • proxalutamide (GT0918)
over2years
Selective targeting of PARP-2 inhibits androgen receptor signaling and prostate cancer growth through disruption of FOXA1 function. (PubMed, Proc Natl Acad Sci U S A)
Next-generation antiandrogens act through inhibiting androgen synthesis (abiraterone) or blocking ligand binding (enzalutamide). Selective targeting of PARP-2, however, may provide an alternative therapeutic approach for AR inhibition by disruption of FOXA1 function, which may be beneficial to patients, irrespective of their DNA-repair deficiency status.
Journal • PARP Biomarker
|
AR (Androgen receptor)
|
DDR • AR positive
|
enzalutamide capsule • abiraterone acetate
over2years
Bicalutamide in Treating Patients With Metastatic Breast Cancer (clinicaltrials.gov)
P2, N=28, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Mar 2020 --> Mar 2021 | Trial primary completion date: Mar 2020 --> Mar 2021
Clinical • Trial completion date • Trial primary completion date
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
AR positive • PGR negative
|
bicalutamide
over2years
Determination of the androgen receptor status of circulating tumour cells in metastatic breast cancer patients. (PubMed, BMC Cancer)
In 43% of the analysed CTC samples from patients with MBC the AR expression has been detected. The predictive value of AR expression in CTCs remains to be evaluated in further trials.
Clinical • Journal • Circulating Tumor Cells
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
|
AR positive • AR expression
over2years
BCL11A confers cell invasion and migration in androgen receptor-positive triple-negative breast cancer. (PubMed, Oncol Lett)
Moreover, BCL11A-knockdown significantly inhibited the expression level of AR and further had an influence on proliferation, migration and invasion in TNBC cell lines. Collectively, the results of the current study indicate the function of BCL11A in TNBC progression, and provide new insights into the unique mechanism of BCL11A in AR regulation, emphasizing the significance of more research on BCL11A and AR regulation in TNBC molecular treatment.
Journal
|
AR (Androgen receptor)
|
AR positive
over2years
Novel dual BET and PLK1 inhibitor WNY0824 exerts potent anti-tumor effects in CRPC by inhibiting transcription factor function and inducing mitotic abnormality. (PubMed, Mol Cancer Ther)
In vivo, oral WNY0824 administration suppressed tumor growth in the CRPC xenograft model of enzalutamide resistance. These findings suggest that WNY0824 is a selective dual BET and PLK1 inhibitor with potent anti-CRPC oncogenic activity and provides insights into the development of other novel dual BET- and PLK1-inhibiting drugs.
Journal
|
AR (Androgen receptor)
|
AR positive
|
enzalutamide capsule
over2years
NF-κB signaling promotes castration-resistant prostate cancer initiation and progression. (PubMed, Pharmacol Ther)
Whether CRPCa is due to aberrant AR activity or AR independence, NF-κB signaling is also implicated in the initiation and maintenance of CRPCa and, thus, the NF-κB pathway may be a promising alternative therapeutic target. In this review, we present evidence that NF-κB signaling promotes CRPCa initiation and progression, describe the dichotomic role of NF-κB in the regulation of AR expression and activity and outline studies that explore NF-κB inhibitors as PCa therapies.
Review • Journal
|
AR (Androgen receptor)
|
AR positive
over2years
Shh Overexpression Is Correlated with GRP78 and AR Expression in Primary Prostate Cancer: Clinicopathological Features and Outcomes in a Chinese Cohort. (PubMed, Cancer Manag Res)
Shh is overexpressed in high-grade prostate cancer and is positively correlated with the expression of both GRP78 and AR. Therefore, Shh may be a useful prognostic marker and therapeutic target for prostate cancer.
Clinical • Journal
|
AR (Androgen receptor)
|
AR positive
over2years
Glycogen-rich Clear Cell Carcinoma of the Breast: A Comprehensive Review. (PubMed, Appl Immunohistochem Mol Morphol)
Because of its rarity, the prognosis for GRCC patients remains controversial. Herein, we comprehensively appraise the epidemiological, morphologic, molecular, and clinical characteristics of this rare mammary malignancy.
Journal
|
PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • AR (Androgen receptor)
|
EGFR expression • AR positive • AR splice variant 7
over2years
Seviteronel, a Novel CYP17 Lyase Inhibitor and Androgen Receptor Antagonist, Radiosensitizes AR-Positive Triple Negative Breast Cancer Cells. (PubMed, Front Endocrinol (Lausanne))
Enzalutamide and seviteronel treatment also had different effects on AR and AR target genes as measured by immunoblot and qPCR. These results implicate AR as a mediator of radioresistance in AR+ TNBC models and support the use of seviteronel as a radiosensitizing agent in AR+ TNBC.
Journal
|
ER (Estrogen receptor) • AR (Androgen receptor)
|
AR positive • AR expression
|
enzalutamide capsule • seviteronel (INO-464)
over2years
Harnessing Androgen-Receptor Pathway Activation for Targeted Alpha Particle Radioimmunotherapy of Breast Cancer. (PubMed, Clin Cancer Res)
[225Ac]hu11B6 targeted radiotherapy was potentiated by DHT and by D-Norgestrel in murine xenograft models of BCa. AR activity in BCa correlates with kallikrein related peptidase-2 and can be activated by D-Norgestrel, a common contraceptive, and AR-induction can be harnessed for hK2-targeted BCa a-emitter radiotherapy.
Journal
|
AR (Androgen receptor)
|
AR positive
over2years
Enhancing abiraterone acetate efficacy in androgen receptor-positive triple negative breast cancer: Chk1 as a potential target. (PubMed, Clin Cancer Res)
This study suggests that apocrine features can be helpful in the identification of AA-responders. We identified Chk1 as a putative drug target in AR-positive TNBCs.
Clinical • Journal
|
AR (Androgen receptor)
|
AR positive
|
abiraterone acetate • RG7741
over2years
Molecular apocrine tumours in EORTC 10994/BIG 1-00 phase III study: pathological response after neoadjuvant chemotherapy and clinical outcomes. (PubMed, Br J Cancer)
Irrespective of their HER2 status, the prognosis for MA tumours remains poor and adjuvant trials evaluating anti-androgens should be considered.
Clinical • Clinical data • P3 data • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
|
HER-2 positive • AR positive
over2years
Contribution of Adrenal Glands to Intra-tumor Androgens and Growth of Castration Resistant Prostate Cancer. (PubMed, Clin Cancer Res)
Mice are appropriate for evaluating adrenal impact of steroidogenesis inhibitors. A subset of adrenalectomy-resistant CRPC tumors demonstrate de novo androgen synthesis. Tumor growth and androgens were suppressed more strongly by surgical adrenalectomy than prior studies using abiraterone, suggesting reduction in adrenally-derived androgens beyond that achieved by abiraterone may have clinical benefit. Proof-of-concept studies with agents capable of achieving true 'non-surgical ADX' are warranted.
Journal
|
AR (Androgen receptor)
|
AR positive
|
abiraterone acetate
over2years
Short-term Preoperative Treatment With Enzalutamide, Alone or in Combination With Exemestane in Primary Breast Cancer (clinicaltrials.gov)
P2, N=221, Active, not recruiting, Queen Mary University of London | Trial completion date: Mar 2019 --> Mar 2020 | Trial primary completion date: Mar 2019 --> Mar 2020
Clinical • Trial completion date • Trial primary completion date • Combination therapy
|
HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor) • CASP3 (Caspase 3)
|
AR positive • AR expression
|
enzalutamide capsule • exemestane