AR positive

(Trial registration: ClinicalTrials.gov NCT04159896. Registration date: November 12, 2019.).

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=30, Active, not recruiting, Providence Health & Services | Trial completion date: Apr 2026 --> Jan 2026 | Trial primary completion date: Aug 2024 --> Jan 2025

The present results suggested that hormonal and metabolic dysregulation may be associated with the pathogenesis of SC, and that AR and MCT1 in particular may serve as prognostic indicators and potential therapeutic targets. Additionally, ~10% of SC cases exhibited PD-L1 expression within the druggable range, and these patients are expected to benefit from treatment with immune checkpoint inhibitors.

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

KDM5B-PGC1α is thus a potential therapeutic target for both androgen-sensitive and castration-resistant tumors. Meanwhile, PGC1α overexpression may serve as a useful prognosticator in those undergoing radical prostatectomy.

Combination therapy with enzalutamide and JH-RE-06 significantly suppresses cancer growth in a syngeneic murine tumor model over vehicle control or individual treatment groups. These findings suggest that AR inhibition broadly triggers DNA replication stress in hormone-sensitive prostate cancer, thereby exposing a unique vulnerability that can be exploited by a TLS-disrupting adjuvant for targeted therapy.

P2, N=20, Recruiting, Manish Patel | Trial completion date: Sep 2024 --> Oct 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P1/2, N=37, Recruiting, Kari Wisinski | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

CXCL8, in turn, activated the mTORC1 pathway, which increased de novo cholesterol synthesis by activating sterol regulatory element-binding protein-2 (SREBP2). Together, these results suggested that the CXCL8-mTORC1-SREBP2 axis contributed to the exacerbation of tumorigenicity in AR- PCa cells under androgen-ablative therapies.

The DUCT study addresses an unmet medical need by investigating the repurposing of dutasteride to enhance treatment response and improve clinical outcome for patients with R/M SDC, especially those with limited alternative treatment options, such as HER2-negative cases. By repurposing a registered low-cost drug, this trial's findings could be readily applied into clinical practice.

Moreover, GDNS and its combination with antibody against programed cell death protein 1 (antiPD-1) retarded tumor growth and produced 2.83-fold prolongation of survival in the LAR-positive TNBC model. Therefore, the GSH-disrupting GDNS represents an encouraging strategy to potentiate ferroptosis for treating refractory LAR-subtype TNBC.

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.

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.

We report unique populations of mast cells that show distinct spatial associations with M2 macrophages and regulatory T cells. Our results show disease-specific neighborhoods that are primarily driven by androgen receptor-positive (AR+) stromal cells and identify inflammatory gene networks active in AR+ prostate stroma.

(Trial registration: ClinicalTrials.gov, NCT03456804. Registration date: March 7, 2018).

When SCC was diagnosed, it was often hypo-differentiated and required more attention. Immunostaining for ADP and AR is invaluable for confirming SGC diagnosis.

53.0% and 36.8% had previously received both abiraterone and enzalutamide, and 69.7% and 64.7% had received cabazitaxel in patients with and without AR-LBD mutation respectively. Administration of Opevesostat to heavily pre-treated mCRPC patients shows promising antitumor activity. PSA50 responses were most frequent among patients harbouring activating AR-LBD mutations.

On multivariate analysis, only tumor staging was a significant predictor of survival (p = 0.012) and AR expression of > 10% revealed a trend towards improved survival (p = 0.07). When considering only AR-positive TNBC, AR expression of > 10% (p = 0.038), distant metastases (p = 0.003), and EGFR status (p = 0.024) were significantly associated with survival. AR expression does not seem to very strongly correlate with prognosis in TNBC and further studies could focus more on its predictive role in deciding anti-androgen therapy.

PFS was significantly lower in ERβ-negative group. Further exploratory studies on larger sample sizes are required to validate these findings in NMIBC patients.

Thus, the need of the hour is to target the androgen receptor as a monotherapy or in combination with other conventional therapies which has proven to be an effective clinical strategy for the treatment of prostate cancer patients, and these therapeutic strategies are increasingly being investigated in breast cancer. Therefore, in this manuscript, we review the role of AR in various cellular processes that promote tumorigenesis and aggressiveness, in different subtypes of breast cancer, as well as discuss ongoing efforts to target AR for the more effective treatment and prevention of breast cancer.

Our findings shed light on the genome-wide network of OCT1 and AR in AR-positive CRPC and highlight the potential role of CTBP2 in immune response and tumor progression. Targeting CTBP2 may represent a promising therapeutic approach for aggressive AR-positive CRPC. Further validation will be required to explore novel therapeutic strategies for CRPC management.

Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

P2, N=26, Recruiting, Radboud University Medical Center | N=98 --> 26

Homoharringtonine, a Food And Drug Administration-approved translation elongation inhibitor, impedes CRPC progression in preclinical models and patients with CRPC. We construct an SCLPC-specific signature capable of stratifying patients for drug selectivity. Our studies reveal the existence of SCLPC in admixed PCa pathology, which may mediate tumor relapse, and establish SP1 and translation elongation as actionable therapeutic targets for CRPC.

A combined inhibitor of these three proteins, NEO2734, reduced the growth of both AR-positive and AR-null organoids, as measured by changes in viability, size, and composition..

In this study, we examined the chromatin landscape of AR-positive prostate cancer cells post-exposure to the AR inhibitor enzalutamide...These effects were mediated through the downregulation of the Wnt/β-catenin signalling pathway and subsequent reduction of nuclear β-catenin. Collectively, our findings provide compelling evidence that the depletion of SIX2 may represent a promising strategy for overcoming the cell plasticity mechanisms driving antiandrogen resistance in prostate cancer.

Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.

P2, N=31, Active, not recruiting, Janssen Pharmaceutical K.K. | Trial completion date: May 2024 --> Sep 2025

P1/2, N=37, Recruiting, Kari Wisinski | Trial primary completion date: Jan 2024 --> May 2024

In addition, increased expressions of Nanog, Oct3/4, survivin, and Bcl-2 were observed. Although the molecules we studied have diverse effects on cellular regulation, our data emphasize obesity's multifaceted role in promoting and aggressing PC, notably affecting PCSC populations.

P2, N=88, Recruiting, Fudan University | N=66 --> 88

CBPD-268 was well tolerated in mice and rats and displayed a therapeutic index of >10. Taking these results together, CBPD-268 is a highly promising CBP/p300 degrader as a potential new cancer therapy.

P2, N=22, Terminated, GTx | Completed --> Terminated

In two of the human bladder cancer lines expressing MR, treatment with a natural MR ligand, aldosterone, significantly reduced cell proliferation and migration, which was restored by three MR antagonists clinically used, spironolactone (except colony formation of androgen receptor-positive cells cultured in the presence of androgens), eplerenone, and esaxerenone. These findings suggest that MR signaling functions as a tumor suppressor in urothelial carcinoma and prevents tumor growth. Accordingly, there is a possibility that the concurrent use of anti-mineralocorticoids, particularly eplerenone and esaxerenone, in patients with bladder cancer rather contributes to the promotion of disease progression.

Our findings suggest that AR is the promising target for UTUC treatment, especially in PD-L1-negative cases.

In conclusion, hypoalbuminemia was significantly associated with PRAD and decreased survival, while MWB and necrosis were significantly associated with P-TCC on cytology. These clinicopathologic data may help clinicians differentiate between these tumors ante mortem to guide appropriate treatment and intervention.

Then palliative therapy with capecitabine was introduced. With a relatively sustained quality of life, the response lasted for 15 months.

Expression of AR is not significantly associated with the development of bone metastases in TNBC. However, patients with absent sTILs in their primary tumours are highly susceptible for recurrence in the bone and might particularly benefit from adjuvant bisphosphonates.

P2, N=18, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

P2, N=20, Recruiting, Manish Patel | Trial completion date: Jan 2024 --> May 2024 | Trial primary completion date: Dec 2023 --> Mar 2024