AR positive

In this review, we explore the unconventional tumor-suppressive function of YAP/TAZ and the mechanisms through which they inhibit tumor growth, with an emphasis on recent findings in hormone-regulated cancers and ccRCC. Finally, we discuss the therapeutic implications of these emerging findings for cancer treatment.

P1, N=2, Terminated, Brown University | N=32 --> 2 | Trial completion date: Jan 2032 --> Oct 2025 | Recruiting --> Terminated | Trial primary completion date: Jan 2027 --> Jul 2025; Principal Investigator left institution

P2, N=88, Active, not recruiting, Fudan University | Trial primary completion date: Dec 2025 --> Dec 2026

Mechanistically, VIC-1911 disabled HR-mediated repair of DSBs in otherwise HR-proficient PC cells, leading to a "BRCAness" phenotype and pronounced accumulation of DNA damage and mitotic catastrophe. In summary, our study uncovers what we believe a novel mechanism to functional "BRCAness" by inducing mitotic arrest and highlights VIC-1911 as a promising therapeutic agent for advanced PC, either as a single agent or in combination, sensitizing HR-proficient tumors to PARP inhibitors.

In summary, this study reveals the molecular mechanism by which AKR1C3 is involved in metabolic reprogramming to promote radioresistance in prostate cancer through PKM2/UBE2T. These findings indicate that targeting AKR1C3 has potential for overcoming radioresistance, providing novel insight into the clinical treatment of prostate cancer.

During a mean follow-up of 97.2 months, distant metastasis occurred in 4/62 patients (6.5%) and locally invasive disease in 4/62 (6.5%), with an overall survival rate of 95%. Overall, these findings highlight the biological heterogeneity of SPNs and indicate that, despite a shared molecular background, aggressive behavior is not defined by a single reproducible pathological or molecular feature.

This study highlights heterogeneity in TMPRSS2-ERG fusion dynamics during t-NEPC evolution and suggests a potential association between ERG expression and earlier NE differentiation. This study provides a rare opportunity to analyze paired pre- and post-NEPC tissues, offering valuable insight into the relationship between ERG and TMPRSS2-ERG fusion gene expression and clinical parameters.

Adjuvant treatment included combination chemotherapy, radiotherapy, and dual hormonal therapy with tamoxifen and an AR inhibitor. This case highlights the diagnostic and therapeutic challenges of hormone receptor-positive AC and underscores the importance of comprehensive immunohistochemical profiling for individualized management.

By exploiting commercially available pharmacological inhibitors, we demonstrate that in AR-positive CRPC cell lines, combinatory inhibition of KDM1A and KDM7A leads to a loss of AR and the AR-driven transcriptome, which in turn attenuates cancer-promoting cell phenotypes. These findings highlight the potential of combination-targeted therapies in tackling advanced prostate cancers.

Membranous and nuclear CD24 were expressed in the majority of mCRPC specimens, while NPY expression was more limited. NPY and nuclear CD24 were more highly expressed in AR+ mCRPC than AR- neuroendocrine disease, and nuclear CD24 displayed site-specific expression, suggesting a potential role for nuclear CD24 in promoting AR+ mCRPC.

Ultimately, we could show no significant influence of AR expression on survival. Our findings suggest that AR may serve as a potential biomarker for predicting axillary response in TNBC.

Mechanistically, while stimulation with the AR-agonist R1881 is sufficient to induce nuclear translocation of AR in AR+ TNBC cells, AR inhibition with enzalutamide, apalutamide, or darolutamide blocked AR nuclear translocation. These findings suggest that AR-mediated radioresistance is at least partially due to downstream MAPK/ERK signaling. Together this work builds on the mechanistic understanding of AR-mediated radioresistance in AR+ TNBC which may expose vulnerabilities in resistance to combination treatment with AR inhibition and RT.