Integrating antibody–drug conjugates, multispecific antibodies, targeted protein degradation, and nanomedicine in precision oncology

Molecular engineering, chemical biology, and translational oncology have transformed the landscape of targeted cancer therapies. Antibody-drug conjugates (ADCs) have advanced into clinically validated platforms that combine antigen-specific recognition with potent cytotoxic payloads, supported by innovations in linker chemistry, drug-to-antibody ratio (DAR) optimization, and bispecific or multispecific antigen targeting. Parallel to ADC development, targeted protein degradation (TPD) technologies-proteolysis-targeting chimeras (PROTACs), molecular glues, and emerging lysosomal and autophagy-based degraders enable the catalytic elimination of oncogenic drivers that were previously considered undruggable. Nanomedicine-based delivery enhances therapeutic selectivity, improves pharmacokinetics, and overcomes barriers to intracellular drug transport. Rational combination therapies that integrate these platforms with immune checkpoint inhibitors, kinase inhibitors, and tumor microenvironment (TME)-modulating agents address tumor heterogeneity and adaptive resistance more effectively than monotherapies. This review synthesizes the foundations of ADCs, multispecific antibodies, protein degraders, nanomedicine platforms, targeted small-molecule inhibitors, and their combination strategies. Clinically, the convergence of these modalities promises to extend durable responses to patient populations with refractory, molecularly complex malignancies by enabling individualized, mechanism-driven therapeutic selection.