AR splice variant 7

Of the thirty-two unique ARVs detected, only AR-V7 (present in 14% of patients) was associated with outcomes after salvage RT+ADT (HR for second biochemical failure, 6.2, 95% CI 2.3-16.5, p=0.0003). These results suggest for the first time that AR-V7 may modulate outcomes for localized in addition to metastatic prostate cancer.

We further show that TRACERs can be modularly reprogrammed to recruit alternative repressors, including PRC2. Collectively, these findings establish TRACERs as a generalizable modality to pharmacologically silence undruggable transcription factors through targeted epigenetic reprogramming, offering a powerful new strategy for treating cancers refractory to existing therapies.

We found no association with prostate cancer outcomes. However, in the group of patients whose PSA became undetectable after treatment, a CTC increase after chemotherapy identified men with a higher risk of cancer progression and death.

In CRPC and enzalutamide-resistant models, ITRI-148 robustly suppresses AR signaling and inhibits cell viability, outperforming enzalutamide...In vivo, ITRI-148 demonstrates potent antitumor efficacy in both castrated and hormone-intact CRPC models, supported by favorable pharmacokinetic properties, stability and safety profiles. These findings position ITRI-148 as a promising next-generation AR-targeting agent capable of degrading resistant AR variants and providing durable inhibition of AR signaling in advanced prostate cancer.

This consensus offers practical guidance for clinical integration of CTCs and outlines strategic research priorities to unlock their full potential in precision oncology.

SCAMP3 and EPS8 cooperatively maintain EGFR stability and signaling in prostate cancer cells, playing a critical role in enzalutamide resistance and metastatic progression. Targeting the SCAMP3-EPS8-EGFR axis offers promising therapeutic opportunities for advanced prostate cancer.

Mice received DMSO, abiraterone, or MPT1A160 intraperitoneal injections twice per week...Furthermore, several MPT1A160-suppressed genes exhibited high mutation frequencies in prostate cancer, suggesting their potential role in therapy resistance. MPT1A160 exhibits potent anti-tumor effects by targeting both androgen biosynthesis and epigenetic regulation, offering a novel dual inhibition strategy for overcoming treatment resistance in prostate cancer.

Compared with the combination treatment group of AR and HSP90 inhibitors (enzalutamide and pimitespib), the nano-PROTAC treatment group presented a high tumor growth inhibition value of up to 78% and a median survival extension of 15 days. Nano-PROTACs that simultaneously degrade AR and HSP90 can overcome the resistance of prostate cancer to PSMA- and AR-positive castration-resistant prostate cancer, except for neuroendocrine prostate cancer, which provides a new therapeutic strategy for the treatment of prostate cancer.

Furthermore, we delineated the regulatory functions of the transcription factors BMAL1 and CLOCK in promoting the expression of PER1 and miR-6883-5p, while miR-6883-5p negatively regulates CLOCK expression, thereby impacting the transcription-translation feedback loop (TTFL) of circadian genes. Collectively, these findings uncover a regulatory axis involving circadian rhythm components, miR-6883-5p, AR-V7, and PCa progression, providing new mechanistic insights into treatment resistance in CRPC and highlighting the circadian clock as a potential therapeutic target.

This enhanced understanding of the distinct molecular and clinical profiles of FOLH1-expressing prostate cancers may inform optimization of PSMA-directed treatments.

Yet, clinical analysis revealed no significant differences in overall survival data in prostate cancer patients. The study challenges the existence of an AR-V specific transcriptome responsible for treatment resistance and tumor progression and highlights the need for further investigation into the molecular mechanism by which AR-V proteins route resistance to ARTA treatment.

Our findings demonstrate that ADT induces MIF upregulation, which in turn drives prostate cancer cell proliferation via upregulating AMPD2 expression, eventually contributing to the development of resistance to ADT.