Multi-Mechanistic Androgen Receptor Suppression by Chinese Medicine: A Polypharmacology Strategy Against Castration-Resistant Prostate Cancer
Castration-resistant prostate cancer (CRPC) is lethal because of persistent androgen receptor (AR) signaling, even when patients undergo androgen deprivation therapy. Resistance can arise through intratumoral androgen synthesis, AR overexpression, mutations in the ligand-binding domain, constitutively active splice variants such as AR-V7, and activation of compensatory bypass pathways. Chinese medicine (CM), with its inherent polypharmacology, offers a promising strategy to target multiple AR resistance mechanisms simultaneously. This review summarizes evidence supporting the use of CM-derived compounds, extracts, and formulas to suppress multiple AR mechanisms as a therapeutic strategy against CRPC. It also discusses challenges in clinical translatability, including compositional complexity and bioavailability. CM is a promising approach to overcoming CRPC resistance and warrants standardized formulation development and rigorous clinical validation.