CAS significantly enhanced ABI's cytotoxic efficacy in 22Rv1 cells, as evidenced by synergistic interactions (CI: 0.31-0.71); however, no such synergy was observed in LNCaP cells or with enzalutamide. Docking and molecular dynamics simulations indicated a stable CAS-AKR1C3 interaction, characterized by crucial hydrogen bonding and aromatic stacking within the active site. These results suggest that CAS is a promising chemosensitizer targeting AKR1C3 to overcome ABI resistance in CRPC.

Genetic variation in SULT2A1 may be useful to inform personalized dosing of abiraterone. ClinicalTrials.gov Identifier: NCT01949337.

AA induces ER stress, leading to transcriptional downregulation of the AR and suppression of PCa cell viability and proliferation. Targeting the PERK pathway may enhance AA efficacy in AR-driven PCa.

BRCA1/2-mutant patients benefited from Olaparib plus Abiraterone, while persistent alterations predicted early progression. We recommend unified reporting standards (e.g., variant allele frequency thresholds and panel composition) and prioritized prospective trials to validate high-impact targets. These steps will accelerate the integration of ctDNA into routine precision oncology practice worldwide.

P=N/A, N=40, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed

P=N/A, N=360, Recruiting, Leiden University Medical Center | Not yet recruiting --> Recruiting | Trial completion date: Jul 2027 --> Jul 2028 | Trial primary completion date: Dec 2026 --> Dec 2027

P2, N=140, Not yet recruiting, University of Nebraska

In PROpel, there were no differences in HRQoL or pain scores reported by patients with mCRPC receiving olaparib + abiraterone versus placebo + abiraterone, suggesting that patients can derive a clinical benefit from olaparib + abiraterone while maintaining similar HRQoL in comparison with current standard-of-care treatment. The PROpel trial is registered on ClinicalTrials.gov as NCT03732820.

Results for ORR, DoR, confirmed PSA50-RR, and time to PSA progression favoured Ola + Abi over P + Abi in the ITT population and biomarker subgroups. The data support consideration of Ola + Abi as first-line treatment for mCRPC.

P1, N=4, Terminated, University of Texas Southwestern Medical Center | N=36 --> 4 | Suspended --> Terminated; The study has been affected significantly by the COVID pandemic, drug supply/drug amendment, low recruitment interest, and FDA approval of another drug with the same indication, so this study has not met its primary endpoint data requirements.

Our study suggests a prognostic impact of statin use in the PFS in patients receiving abiraterone or enzalutamide for mCRPC. This may be related to the enhancement of the antitumor activity of the ADT drugs, but also to the cardioprotective effects associated with statin use.

The HSD3B1 germline variant (1245C) is linked to earlier ADT failure and diminished efficacy of abiraterone but does not affect enzalutamide in the treatment of PCa patients. These findings underscore its potential as a biomarker to guide personalized treatment in PCa.