AR and Beyond: ctDNA Maps Resistance Evolution in mCRPC.

Chauhan, Pradeep S; Pachynski, Russell K; Maher, Christopher A; Chaudhuri, Aadel A · Clin Cancer Res · 2026

prospective_cohort · Level II

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Abstract

Longitudinal plasma cfDNA profiling from the phase 3 Alliance A031201 trial revealed divergent resistance trajectories in mCRPC. Rapid progressors harbored non-AR alterations suggesting intrinsic resistance, whereas delayed progressors showed progressive AR amplifications, structural rearrangements and extrachromosomal DNA-associated evolution. These findings support biomarker-guided strategies targeting AR-dependent and AR-independent disease states.