abiraterone acetate

While next-generation androgen receptor signaling inhibitors (ARSIs), such as enzalutamide and abiraterone, have revolutionized CRPC treatment, resistance to these therapies remains a significant challenge, rendering the disease incurable. Compelling evidence further suggests that combining PLK1 inhibition with paclitaxel could serve as an effective therapeutic strategy to overcome resistance in CRPC by targeting microtubule dynamics. This review examines the mechanistic role and broader implications of PLK1 in CRPC treatment, offering valuable insights into potential combination therapies to improve efficacy and patient outcomes.

P=N/A, N=75, Not yet recruiting, AstraZeneca

Materials and This prospective cross-sectional, single-center observational study included 130 patients with metastatic prostate cancer receiving AR-targeted therapies (abiraterone, enzalutamide, or apalutamide/darolutamide). These findings highlight the importance of integrating routine psychosocial assessment and supportive care strategies into clinical practice to optimize patient-centered outcomes. However, given the cross-sectional and exploratory nature of the study, the findings should be interpreted cautiously.

The only CYP17A1 inhibitor available in therapy, abiraterone acetate, faces significant limitations due to its steroidal structure, which causes off-target effects and generates agonistic metabolites that paradoxically stimulate the androgen receptor (AR)...In vitro assay results correlated with a suggested mechanism, showing preferential cytotoxicity toward androgen-dependent LNCaP cells (AR+) while sparing AR-negative lines (DU145, PC3) and healthy human fibroblasts (BJ). Our compounds present a promising starting point for further development of non-steroidal CYP17A1 inhibitors.

We highlight the recent results from the Phase III CAPItello-281 trial (NCT04493853) demonstrating that the addition of capivasertib to abiraterone acetate and androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival in patients with PTEN-deficient mCSPC, leading to the FDA-approval of this regimen. Notable adverse events in the cabavisertib arm included hyperglycemia, diarrhea, and rash. CAPItello-281 addresses a significant unmet need for PTEN-deficient mCSPC, suggesting AKT inhibition as a potential new targeted treatment strategy for a sub-population with poor prognosis.

Fuzuloparib plus AA-P had an acceptable safety profile and showed promising efficacy among mCRPC patients.

P2, N=26, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Recruiting --> Active, not recruiting | Trial primary completion date: Oct 2026 --> Jul 2026

P1, N=60, Active, not recruiting, EMD Serono Research & Development Institute, Inc. | N=141 --> 60

P2, N=200, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028

P1/2, N=1200, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting

Direct AR antagonism enhances functional PSMA availability and increases short-term uptake of PSMA-targeted radioligands in AR-positive prostate cancer models. These findings provide mechanistic support for AR-mediated modulation of PSMA-targeted radioligand delivery and warrant further translational investigation.

P3, N=110, Active, not recruiting, AstraZeneca | Trial completion date: Apr 2026 --> Feb 2027