P3, N=206, Recruiting, Jiangsu HengRui Medicine Co., Ltd. | N=156 --> 206

KIF15 functions as a context-dependent regulator of mitotic adaptation and tumor progression, with reported roles in mitogenic signaling, metabolic reprogramming, and therapeutic resistance across multiple cancer types. Its chemical tractability and non-redundant role in drug-resistant spindle maintenance position it as a compelling candidate for combination anticancer strategies.

This study not only provides mechanistic insights into the role of DUOXA1 in bicalutamide resistance but also highlights the HIF1α-DNMT1-DUOXA1 axis as a critical regulator of resistance. Our work suggests potential therapeutic strategies to overcome resistance through epigenetic modulation and activation of DUOXA1, offering a novel perspective on the molecular mechanisms of bicalutamide resistance and paving the way for the development of improved treatment approaches for advanced prostate cancer.

P3, N=802, Active, not recruiting, University of Sydney | Trial completion date: Mar 2026 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

P1, N=208, Recruiting, Novartis Pharmaceuticals

P3, N=600, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

P1, N=80, Recruiting, University of Wisconsin, Madison | Not yet recruiting --> Recruiting

P1/2, N=20, Recruiting, University of Michigan Rogel Cancer Center | N=39 --> 20

P2, N=32, Not yet recruiting, Medical College of Wisconsin | Initiation date: Mar 2026 --> Jul 2026

P2, N=7, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2029 --> Oct 2026 | Trial primary completion date: Apr 2029 --> Oct 2026

A Phase Ib clinical trial (NCT03751436) combining enzalutamide and BCL-2 inhibitor venetoclax demonstrated reduced circulating tumor cells in responding patients. In summary, by integrating high-content single-cell level imaging analyses with mechanistic studies, extensive preclinical therapeutic experiments and a Phase Ib clinical trial, our studies herein elucidate the AR+/-BCL-2+/- PCa cell subpopulation dynamics and credentials BCL-2 as a vital therapeutic target in heterogeneous CRPC.

PSMA PET-derived volumetric parameters, particularly PSMA tumor volume, provide robust prognostic information in mCRPC patients treated with abiraterone or enzalutamide. When combined with early PSA kinetics, these imaging biomarkers enable improved risk stratification and may support more individualized treatment strategies. Prospective multicenter studies are warranted to validate these findings.