Targeting Biliary Tract Cancers with Antibody–Drug Conjugates: Advances in Molecular Targets and Rational Combinations

Antibody-drug conjugates (ADCs), an emerging targeted treatment method, are designed to couple the tumor selectivity of monoclonal antibodies with the cytotoxic potency of small-molecule payloads, thereby offering an accurate approach for biliary tract cancers (BTCs). BTC is characterized by typical molecular heterogeneity, a desmoplastic stroma, and an immune-suppressive microenvironment, which together limit the efficacy of conventional chemotherapy and weaken responses to immunotherapy in unselected patients. The demand for drugs that can improve the survival rate of BTC patients has not yet been met. The evaluation of ADC therapy for BTC has become a focus of extensive clinical and preclinical research, and encouraging preliminary results have been achieved. In this review, we comprehensively summarize the increasing body of evidence regarding the application of ADCs in BTC relative trials. Starting with a brief discussion of the functional principles of ADCs, we summarize the trials of different designs of ADCs in BTC, as well as the relevant clinical data related to ADC-based combination therapy regimens.