AR expression

Although treatment of GCT in transgender individuals has not been well-described, the impact of exogenous hormone use on cancer physiology and treatment should be considered, while also addressing gender dysphoria throughout treatment and in surveillance. Here, we describe a FTM transgender patient with recurrent AR-positive adult granulosa cell tumor after starting testosterone supplementation, along with a literature review to explore the current knowledge of ovarian changes observed following FTM gender transition and subsequent risk of ovarian cancer.

AR expression may be related to good prognostic factors such as ER expression, PgR expression, and lower histologic grade. We also observed that AR expression did not have any association with the Ki67 proliferative index.

P2, N=149, Completed, European Organisation for Research and Treatment of Cancer - EORTC | Active, not recruiting --> Completed | Trial completion date: Jul 2024 --> Feb 2024

We then propose and experimentally validate an unbalanced multi-enhancer model where the impact on gene expression of AR-bound enhancers is heterogeneous, and is proportional to their contact frequency with target gene promoters. Overall, these findings provide insights into AR-mediated gene expression upon acute androgen simulation and develop a mechanistic framework to investigate nuclear receptor mediated perturbations.

Our findings demonstrate that GOLM1 enhances ubiquitin proteasome activity by binding to PSMD1, thereby facilitating AR-driven transcriptional activity and PCa progression. These results indicate that GOLM1 and its associated proteins may become potential therapeutic targets for PCa characterized by dysregulated AR-driven transcriptional activation.

MYO6 has pro-tumor and Enz-resistant effects in CRPC, suggesting that targeting MYO6 may be beneficial for ENZ-resistant CRPC therapy through the AR/MYO6/FAK signaling pathway.

Collectively, our study establishes PYGB as a direct target of AR that assumes an indispensable role in both tumor progression and metabolic reprogramming affiliated with ESCC, thus paving novel avenues for therapeutic strategies centered on metabolic intercessions.

P=N/A, N=0, Withdrawn, Brigham and Women's Hospital | N=20 --> 0 | Trial completion date: Oct 2026 --> Nov 2029 | Not yet recruiting --> Withdrawn | Trial primary completion date: Oct 2025 --> Nov 2028

Transcriptomes distinguished ETS -fused tumors from SPOP mutants, and PTEN loss from PTEN/AKT1 mutations. Inferred relationships between specific genomic alterations and gene expression signatures of luminal/basal subtypes and of biological pathways/processes, including AR signaling, proliferation, and plasticity signatures, provide a basis to understand differences in treatment response and inform biomarker-guided treatment strategies.

P2, N=31, Active, not recruiting, Janssen Pharmaceutical K.K. | Trial completion date: Sep 2025 --> Dec 2027

Silencing XRCC3 exerts anti-PCa effects by promoting DNA damage-induced p53/Bax signaling pathway activation in an AR expression-independent manner.

These findings demonstrate that Abi + Chl treatment lowers autophagy levels and suppresses tumors more effectively than Abi alone.

A driver role of the FGFR3::TACC3 fusion in the first category (as a potential distinct entity) remains to be further studied. In the light of available FGFR-targeting therapies, delineation of these tumors and enhanced recognition is recommended.

Here, we summarize the latest discoveries of stromal AR niches and their interactions with prostatic epithelia. In combination with emerging clinical and experimental evidence, we specifically discuss several important and long-term unanswered questions regarding tumor niche roles of stromal AR and highlight future therapeutic strategies by co-targeting epithelial and stromal AR for treating advanced PCa.

The trial registration number is NCT02955394. The full trial protocol is available under Study Details at the Clinicaltrials.gov link provided).

Systemic treatments contribute to the survival of patients with salivary gland cancer at relapsed or newly advanced stages. The response to treatment is heavily influenced by histological subtype and treatment specificity.

AR-overexpression and its association with other genes could favor a transcriptomic signature set to aid in identifying patients suitable for TKI in monotherapy, rather than aggressive combinations, enhancing thus, precision and personalized therapeutic decisions.

Mechanistically, AR promotes cell proliferation and PRL secretion and confers drug resistance by transcriptionally regulating NRF2 expression to maintain redox homeostasis in PA cells. Finally, combining AR targeting agents with BRC shows promise as a therapeutic strategy for treating PRL adenomas.

When analyzing pioneer transcription factors, the AMPC lesion exhibited elevated FOXA1 activity while the brain NEPC lesion showed elevated HOXC10, NFYB, and OTX2 expression suggesting novel roles in NEPC formation or brain tropism. Our results highlight the utility of performing multi-omic characterization, especially in rare cancer subtypes.

Sex hormones and their receptors are implicated in the pathogenesis of CKS in Xinjiang. The use of ER antagonists may represent a novel avenue for research and treatment of CKS.

By revealing the steroid landscape of bladder cancer, our study not only underscores the androgen-poor nature of the malignancy but also identifies potential alterations in steroid profiles that are linked to disease aggressiveness.

DHT enhances the immune response against EBVaGC by upregulating MICA and activating NK and T cells. These findings suggest potential therapeutic strategies targeting androgen signaling to improve anti-tumor immunity in EBVaGC.

Higher AR expression levels are associated with higher grade disease and histopathologic features predicting poorer prognosis in lower grade gliomas. Higher gene expression in LGG patients is correlated with poor prognosis but not in the glioblastoma cohort suggesting saturated expression/functions of AR in glioblastoma.

These findings indicate that persistent activation of a context-dependent tumor suppressor may lead to resistance through lineage plasticity-driven tumor metamorphosis. Our work provides a framework to explore the above phenomenon across multiple cancer types and underscores the importance of factoring sensitization of tumor suppressor targets while developing agonist-like drugs.

A. pluriseta extracts inhibited DU-145 cell growth without causing cellular toxicity, suggesting great potential for development as an anti-prostate cancer agent. However, further in vitro and in vivo experiments are recommended.

Number of testicular blood vessels were approximately 2-times increased by upregulation of matrix metallopeptidase 2 in TAMs and upregulation of AR expression in the nucleus of Leydig cells. Moreover, we found that the tumor-supportive environment can also be generated even though NOAEL BPA concentration due to the individual's variability in cancer susceptibility.

P2, N=36, Completed, OHSU Knight Cancer Institute | Active, not recruiting --> Completed

We provide evidence that BCL2 expression is regulated by DNA methylation, associated with epithelial-mesenchymal transition, and increased by the neuronal transcription factor ASCL1. Finally, BCL2 inhibition had antitumor activity in some, but not all, BCL2-positive PC models, highlighting the need for combination strategies to enhance tumor cell apoptosis and enrich response.

In conclusion, 18β-GA considerably decreased the uptake of DHEAS and androgen production in cells by inhibiting the transport function of OATP2B1, while ENZ inhibited the nuclear translocation of AR and reduced the expression of AR. The combination of 18β-GA and ENZ can simultaneously inhibit androgen production and AR expression and exhibit a synergistic effect against castration and prostate cancer progression.

CDK8/19 inhibition significantly decreased PSA secretion in LNCaP and 22Rv1 cells and, when combined with enzalutamide, additively reduced proliferation in 22Rv1 cells. Our study revealed that MED12 and CDK8/19 regulate AR activity and that their inhibition may modulate response to enzalutamide in prostate cancer.

Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.

Inhibition or overexpression of miR-1271-5p levels affects prostate cancer cell growth, apoptosis and expression of both androgen receptor target genes and other genes that are likely direct targets, dependent on androgen receptor status, and tumour stage. We conclude that miR-1271-5p has the potential to drive progression of hormone-dependent disease and that the use of specific inhibitors of miR-1271-5p may have therapeutic potential in prostate cancer.

Moreover, LPHN3 positivity in muscle-invasive bladder tumors, as an independent prognosticator, was associated with a significantly higher risk of disease progression and disease-specific mortality following radical cystectomy. These findings suggest that LPHN3 functions as a downstream effector of AR and promotes the growth of bladder cancer.

Liquid biopsy gives an early indication of docetaxel futility, could guide patient selection for continuing enzalutamide, and identifies cell cycle gene alterations as a potential cause of docetaxel resistance in mCRPC.

Our study identified and established methods for culturing human CriPCSCs, which had high tumorigenicity in vivo without any genetic modification or UGSM co-transplantation. Human CriPCSCs differentiated into amplifying adenocarcinoma cells of luminal phenotype in the fast-growing tumors in vivo, which hold the potential to dedifferentiate into intermediate stem cells. These cells resisted castration by upregulating AR expression. The human CriPCSC and PrDX methods hold significant potential for advancing prostate cancer research and precision medicine.

AR expression can serve as a reliable basis for judging the clinical molecular types and poor prognosis for breast cancer. AR may be a novel biomarker and target in AR-positive breast cancer depending on significant difference in AR expression among different molecular types of breast cancer.

Herein, we investigated combined blockade of the CDK4/6 and PI3K signaling with palbociclib, alpelisib, and capivasertib, which inhibit CDK4/6, PI3Kα, and AKT1-3, respectively...The AR antagonist enzalutamide was inactive against MDA-MB-453, MFM-223, and CAL148 cells and did not enhance the efficacy of either combination...Finally, treatment with palbociclib and the PDGFR inhibitor CP637451 arrested growth of MDA-MB-453 and MFM-223 cells to the same degree as palbociclib/capivasertib. These findings support testing the combination of CDK4/6 and AKT inhibitors in patients with LAR TNBC, and further investigation of PDGFR antagonists in this breast cancer subtype.

Adding the CDK4/6 inhibitor palbociclib enhanced the antitumor activity of EP0062 or fulvestrant in ESR1-mutant models but not in HER2-enriched or PTEN-mutant PDX models...EP0062 triggers an E2F1 downmodulation which mediates a potent antiproliferative activity. For EP0062-resistant tumors that remain ER-driven, the addition of palbociclib displays a potent antitumor effect.

In conclusion, our study demonstrated that TRPS1 is a highly sensitive marker for most special types of breast carcinoma. TRPS1 was positive in 63.73% of apocrine carcinomas. TRPS1 and AR expression was inversely correlated in TNBC.

Conversely, high dose androgens facilitate the formation of AR dimers/oligomers to suppress c-MYC expression, inhibit proliferation and drive a transcriptional program associated with a differentiated phenotype. These findings highlight the inherent liabilities in current approaches used to inhibit AR action in PCa and are instructive as to strategies that can be used to develop new therapeutics for this disease and other androgenopathies.

© RSNA, 2024 Supplemental material is available for this article. See also the editorial by Rauch in this issue

Interestingly, antioxidants such as N-Acetylcysteine (NAC) and Glutathione (GSH) effectively negated the oxidative stress induced by VK3-OCH3 on PCa cell lines derived from African American patients...In addition, Western blot analysis showed that VK3-OCH3 reduces the expression of androgen receptor, TRX2, and anti-apoptotic signaling molecules such as Bcl-2 and TCTP in the MDA-PCa-2b metastatic PCa cellular model. In conclusion, our results suggested that VK3-OCH3 is a promising anticancer agent that could potentially reduce the mortality rates of African American PCa patients, warranting further preclinical and translational studies.