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.

P1/2, N=39, Recruiting, University of Michigan Rogel Cancer Center | Trial completion date: Oct 2029 --> Jan 2030 | Trial primary completion date: Oct 2027 --> Jan 2028

To functionally validate this finding, we employed lipid nanoparticle (LNP)-mediated co-delivery of si-circPPFIA2 and enzalutamide, which effectively restored drug sensitivity and inhibited tumor growth in resistant PCa models. Our findings highlight circPPFIA2 as both a prognostic biomarker and a promising therapeutic target for advanced PCa, providing a rationale for developing circRNA-directed therapies to overcome treatment resistance.

P=N/A, N=1300, Completed, Pfizer | Recruiting --> Completed

P=N/A, N=600, Recruiting, Bayer | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Mar 2026 --> Mar 2028

Similarly, targeting SphK1 with the inhibitor SKI-II suppressed SphK1 activity, reduced S1P production, enhanced enzalutamide sensitivity, and significantly inhibited resistant tumor growth while enhancing enzalutamide sensitivity. Collectively, these findings highlight IGFBP3-mediated SphK1 signaling as a critical mediator of enzalutamide resistance and suggest that targeting the IGFBP3/SphK1/S1P axis represents a promising therapeutic strategy to overcome resistance in advanced prostate cancer.

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

P2, N=58, Active, not recruiting, OHSU Knight Cancer Institute | Trial completion date: Jun 2025 --> Jun 2026

LNCaP and VCaP cells were treated with enzalutamide (0.1-10 µM) for 1-7 days...Crucially, ER stress markers correlated with PSMA trafficking, suggesting serum-based profiling could enable individualized ARB adjustments. Future studies should validate these biomarkers to establish personalized ARB-RLT strategies for improved clinical outcomes.

Sixteen-week-old BALB/c mice received enzalutamide, a nonsteroidal antiandrogen, at 50 mg/kg/day via oral gavage 5 days a week for 8 weeks to simulate the ADT protocol...These results suggest that blood could be a valuable source of biomarkers for ADT-induced cognitive dysfunction. Further studies are needed to assess their clinical applicability in monitoring cognitive decline in prostate cancer patients on ADT and in neurotypical aging.

The low-risk group exhibited improved survival outcomes and increased sensitivity to immunotherapy, whereas the high-risk group showed heightened sensitivity to to bexarotene, bicalutamide, embelin, FH535, and pazopanib. Quantitative PCR results indicated that ILF3-DT and PPP1R14B-AS1 were downregulated in CC tissues, whereas RUSC1-AS1 was upregulated. In conclusion, we developed a novel prognostic risk signature based on 9 disulfidptosis-related lncRNAs, which may serve as an independent predictor of immunotherapy response and chemotherapy sensitivity in CC.

Pharmacological inhibition of NSD2 with a first-in-class small molecule reverses plasticity and synergizes with enzalutamide to suppress growth and promote cell death in human patient-derived organoids of multiple CRPC subtypes in culture and in xenografts. Co-targeting of NSD2 and AR may represent a new therapeutic strategy for lethal forms of CRPC that are currently recalcitrant to treatment.