Past, present and future of drug conjugates for cancer therapy

Drug conjugates have emerged as promising tumor-targeted cytotoxics with an improved therapeutic index compared to classical chemotherapeutics. Although traditionally based on antibody ligands, high-throughput screening methods, such as peptide display and DNA-encoded chemical libraries, have enabled the isolation of ultra-high-affinity small ligands and the generation of drug conjugates with better tumor-targeting performance. This Perspective examines the history, major clinical milestones and future of drug conjugates for cancer treatment. We also discuss a new wave of combination modalities, linker strategies, and the development of conjugates based on large and small delivery vehicles. Neri and colleagues discuss the development of drug conjugates for cancer therapy, focusing on current and future opportunities to improve tumor-targeting efficacy with small molecule–drug conjugates and combination therapies.