Xtandi (enzalutamide)

P1/2, N=52, Recruiting, Weill Medical College of Cornell University | Active, not recruiting --> Recruiting | N=37 --> 52

P4, N=43, Active, not recruiting, AstraZeneca | Completed --> Active, not recruiting | Trial completion date: Jul 2025 --> Dec 2026

P2, N=532, Recruiting, Mayo Clinic | Trial completion date: May 2029 --> Feb 2031 | Trial primary completion date: May 2029 --> Feb 2031

Key advances include: (1) In bladder cancer, perioperative durvalumab (NIAGARA) and enfortumab vedotin plus pembrolizumab (KEYNOTE-905/EV-303) set new standards, while HER2-targeted disitamab vedotin plus toripalimab (RC48-C016) improved metastatic survival...(3) In prostate cancer, enzalutamide plus leuprolide improved survival in high-risk biochemical recurrence (EMBARK). Capivasertib plus abiraterone benefited PTEN-deficient metastatic hormone-sensitive disease (CAPItello-281). The PSMAddition trial demonstrated that adding [177Lu]Lu-PSMA-617 to standard therapy significantly improved radiographic PFS in PSMA-positive mHSPC. Docetaxel scheduling was optimized (ARASAFE), and an AI model (STAMPEDE) identified patients for AR inhibitor benefit. Novel agents like saruparib and pasritamig showed promise...The 2025 evidence establishes multiple new standards of care across GU cancers, emphasizing biomarker-driven strategies, immunotherapy integration, novel resistance mechanisms, and treatment optimization. This synthesis provides an evidence-based framework for updating guidelines and highlights the move toward more personalized management, while noting persistent challenges and future research needs.

MAICs showed improved clinical benefit with TALA+ENZA versus OLAP+AAP and NIRA+AAP across multiple mCRPC populations and endpoints. Despite limitations of indirect comparisons, findings support TALA+ENZA as a first-line treatment option for mCRPC.

P1, N=15, Completed, Janssen Research & Development, LLC | Active, not recruiting --> Completed | Trial completion date: Oct 2037 --> Mar 2026 | Trial primary completion date: Oct 2037 --> Mar 2026

Mechanistically, ubiquitin-specific protease (USP7) enhanced the stability of WTAP by the ubiquitin-proteasome pathway in ENZR cells, thereby WTAP increases promote AKT signaling through an m6A-mediated way, and an AKT inhibitor can abolish the pro-resistance phenotype mediated by WTAP. Together, these findings suggest that WTAP plays a key role in ENZR development of PCa cells, and WTAP may be a potential treatment target for ENZR tumors.

P1/2, N=39, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Jan 2030 --> Jun 2030 | Trial primary completion date: Jan 2028 --> Jun 2028

Approximately 1800 participants (550 HRRm; 1250 non-HRRm) are randomized 1:1 to receive either saruparib plus physician's choice of ARPI (abiraterone plus prednisone/prednisolone, darolutamide, or enzalutamide) or placebo plus ARPI. Analyses of rPFS and OS will be conducted within each cohort by stratified log-rank test. Enrollment began in November 2023.Clinical trial registration: www.clinicaltrials.gov identifier is NCT06120491; EU CT number is 2023-504214-30-00.

These findings provide preclinical evidence supporting the combined application of GBQY and enzalutamide in CRPC treatment. By elucidating the interaction between Traditional Chinese Medicine (TCM) and conventional anti-tumor therapy within TME, this study offers mechanistic insights into resistance modulation and paves the way to optimizing the precision of TCM-based therapeutic strategies in PC management.

In CD44+ PCSCs, HA-SeNP-Api produced the strongest cytotoxicity in the MTT assay (14.61% viability), exceeding the effects of apigenin, enzalutamide, SeNP, and non-targeted SeNP-Api (HA-)...Intracellular ROS profiling further indicated redox modulation by SeNP-containing formulations, with partial attenuation by NAC, supporting a ROS-linked contribution to the observed apoptotic response. Collectively, HA-SeNP-Api integrates CD44-mediated targeting with redox-driven stress signaling to achieve potent anti-PCSC activity, supporting further preclinical evaluation.

Functionally, RBM15 overexpression reduces PCa cell sensitivity to enzalutamide, whereas its knockdown suppresses tumor growth and invasion...Collectively, our findings establish RBM15 as a central epitranscriptomic driver of CRPC and identify the RBM15-DDB1-AR axis as a promising therapeutic target. Dual inhibition of RBM15 and AR may offer a novel strategy to overcome treatment resistance in advanced PCa.