Xtandi (enzalutamide)

Increasing interest in AR biology has led to the evaluation of several anti-androgen therapies in AR-positive TNBC, including agents such as enzalutamide, enobosarm, orteronel, bicalutamide, and seviteronel. Although clinical activity has generally been modest, these studies highlight the potential relevance of AR-targeted strategies in selected patient subgroups. This review summarizes current knowledge on androgen and AR signaling in TNBC, integrating molecular mechanisms, preclinical evidence, and clinical studies, and discusses emerging therapeutic strategies aimed at improving patient treatment outcomes.

KIF15 functions as a context-dependent regulator of mitotic adaptation and tumor progression, with reported roles in mitogenic signaling, metabolic reprogramming, and therapeutic resistance across multiple cancer types. Its chemical tractability and non-redundant role in drug-resistant spindle maintenance position it as a compelling candidate for combination anticancer strategies.

P2, N=200, Recruiting, Zenith Epigenetics | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Dec 2025 --> Dec 2026

P1/2, N=40, Enrolling by invitation, Zenith Epigenetics | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Dec 2027

P3, N=802, Active, not recruiting, University of Sydney | Trial completion date: Mar 2026 --> Jun 2026 | Trial primary completion date: Jun 2025 --> Jun 2026

P2, N=100, Recruiting, Hoffmann-La Roche

P1, N=208, Recruiting, Novartis Pharmaceuticals

P3, N=600, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

P1/2, N=20, Recruiting, University of Michigan Rogel Cancer Center | N=39 --> 20

P3, N=1310, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Aug 2028 --> Feb 2030

P2, N=7, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2029 --> Oct 2026 | Trial primary completion date: Apr 2029 --> Oct 2026

A Phase Ib clinical trial (NCT03751436) combining enzalutamide and BCL-2 inhibitor venetoclax demonstrated reduced circulating tumor cells in responding patients. In summary, by integrating high-content single-cell level imaging analyses with mechanistic studies, extensive preclinical therapeutic experiments and a Phase Ib clinical trial, our studies herein elucidate the AR+/-BCL-2+/- PCa cell subpopulation dynamics and credentials BCL-2 as a vital therapeutic target in heterogeneous CRPC.