Taxane therapy in mCRPC: current positioning and emerging strategies to overcome resistance.

Abstract

Introduction: Metastatic castration-resistant prostate cancer (mCRPC) remains a major cause of prostate cancer-related mortality. Taxane-based chemotherapy, including docetaxel and cabazitaxel, remains an important treatment option despite the expanding use of androgen receptor signaling inhibitors (ARSIs), poly(ADP-ribose) polymerase (PARP) inhibitors, and prostate-specific membrane antigen (PSMA)-targeted radioligand therapy.

Areas covered: A structured literature search was conducted in PubMed/MEDLINE, Web of Science, and ClinicalTrials.gov from inception to March 2026. This review summarizes the evolving clinical role of docetaxel and cabazitaxel in mCRPC and briefly outlines the biological mechanisms underlying taxane activity and resistance as a rationale for therapeutic development. Particular emphasis is placed on investigational strategies designed to delay or overcome taxane resistance, including AR pathway-directed combinations, platinum-taxane strategies, PI3K/AKT/mTOR- and other pathway-directed combinations, immunotherapy or radiopharmaceutical combinations, and preclinical resistance-directed approaches. Treatment sequencing, toxicity, quality of life, evidence maturity, and biomarker-informed patient selection are also discussed.

Expert opinion: Taxane resistance is biologically heterogeneous and incompletely captured by current biomarkers. Cabazitaxel after prior docetaxel and early ARSI progression remains the most established sequencing strategy, whereas most resistance-directed approaches remain investigational. Future progress will depend on molecular and imaging-based selection, rational early-phase trial design, and mechanism-informed taxane combinations.