Xtandi (enzalutamide)

P1, N=35, Active, not recruiting, University of Chicago | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

P3, N=296, Recruiting, University College, London | N=76 --> 296

P1/2, N=174, Active, not recruiting, Monte Rosa Therapeutics, Inc | Recruiting --> Active, not recruiting

P2, N=49, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: May 2030 --> Dec 2026 | Trial primary completion date: Apr 2028 --> Dec 2026

P2, N=26, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Dec 2025 --> Oct 2026

Furthermore, inhibition of UHRF1 restored AR pathway activity and re-sensitized resistant prostate cancer cells to enzalutamide. Therefore, our findings elucidate an intracellular molecular mechanism that promotes prostate cancer lineage plasticity and suggest that UHRF1 may serve as a potential therapeutic target for overcoming resistance to AR-targeted therapies.

The patient was started on androgen deprivation therapy with goserelin (10.8 mg every 3 months) and bicalutamide (50 mg once daily), and stable disease was achieved for 66 months...Bicalutamide was replaced by enzalutamide (160 mg once daily) in the treatment regimen. Subsequently, based on the identification of CDK12 mutations by genetic testing, treatment with the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib (300 mg twice daily) was initiated. To date, the patient has remained clinically stable with low PSA levels. This case highlights the potential utility of molecular profiling and combined PARP inhibition and androgen receptor-targeting therapy in CDK12-mutated metastatic castration-resistant PCa with rare penile metastasis.

P1/2, N=76, Recruiting, Novartis Pharma AG | Not yet recruiting --> Recruiting

P=N/A, N=168, Completed, First Affiliated Hospital of Wenzhou Medical University

P1/2, N=37, Active, not recruiting, OHSU Knight Cancer Institute | Trial completion date: Jan 2026 --> Jan 2027

Mechanistically, while stimulation with the AR-agonist R1881 is sufficient to induce nuclear translocation of AR in AR+ TNBC cells, AR inhibition with enzalutamide, apalutamide, or darolutamide blocked AR nuclear translocation. These findings suggest that AR-mediated radioresistance is at least partially due to downstream MAPK/ERK signaling. Together this work builds on the mechanistic understanding of AR-mediated radioresistance in AR+ TNBC which may expose vulnerabilities in resistance to combination treatment with AR inhibition and RT.

Acquired resistance to enzalutamide (Enz) presents a significant challenge in castration-resistant prostate cancer (CRPC), and overcoming this resistance remains an unmet clinical need...Targeting PDHA1 significantly restores cuproptosis and sensitizes CRPC cells to Enz treatment. These findings underscore the potential of PDHA1 inhibition to counteract Enz resistance by reactivating cuproptosis, offering a promising therapeutic approach for treating refractory prostate cancer.