Mechanisms of resistance to antibody-drug conjugates in bladder cancer.

Antibody-drug conjugates (ADCs) have made important advances in the treatment of bladder cancer (BC) in recent years and have demonstrated significant clinical benefit in locally advanced or metastatic urothelial carcinoma (UC). However, the emergence of resistance remains a key factor limiting the durability of their therapeutic efficacy. Current evidence indicates that resistance to ADCs in BC is a complex process driven by multiple tumor-intrinsic and tumor-extrinsic factors. This review systematically summarizes the major mechanisms underlying ADC resistance in BC and outlines potential strategies to overcome it, including the development of next-generation ADCs, combination therapies, and predictive biomarkers. A deeper understanding of BC-specific mechanisms of ADC resistance will help promote the development of more precise and individualized ADC-based treatment strategies.