Antibody-drug conjugates in precision oncology

Antibody-drug conjugates (ADCs) represent a growing therapeutic class in oncology marked by several transformative clinical successes. However, these exceptional outcomes remain restricted to a limited number of tumor types, and ADC development has been marked by frequent clinical setbacks, underscoring persistent challenges in optimal patient selection, biomarker assay standardization, chemical design, and the limited predictive value of existing preclinical models. Despite broader advances in precision oncology, ADC development has largely occurred without validated biomarkers. Emerging evidence indicates that ADC activity extends beyond target antigen expression alone, encompassing tumor-intrinsic features and tumor microenvironment-dependent processes. This challenges the view of ADCs as strictly targeted agents and supports their conceptualization as tumor-ecosystem-targeting therapies governed by multidimensional biological determinants. In this review, we link ADC successes and setbacks to mechanisms of efficacy, resistance, and toxicity, and discuss how biomarkers, ADC combinations, next-generation platforms, and curative-intent strategies should shape precision oncology frameworks.