Cancer-targeting drug conjugates drives a new era in precise cancer treatment

Cancer is the second leading cause of death globally. Its treatment remains a major challenge due to the disease's complexity, heterogeneity, and adaptive nature. Among the array of available treatments, targeted therapy emerges as a paramount approach to address this substantial unmet clinical need, owing to its precise tumor targeting capabilities and potential for mitigating tumor progression risks. Drug conjugates are in high demand for targeted therapy due to their unique ligand specificity and potent cytotoxicity, thereby significantly enhancing therapeutic efficacy and reducing the incidence of adverse effects. Therefore, as a burgeoning field in biomedical research, it is timely to outline the latest advances in drug conjugates-driven cancer treatment. Herein, we aim to present the emerging breakthroughs in this exciting field at the intersection of target ligands, linkers, payloads, and cancer treatments. This review focuses on several drug conjugates-related strategies, including antibody-drug conjugates (ADCs), peptide-drug conjugates (PDCs), small molecule-drug conjugates (SMDCs), aptamer-drug conjugates (ApDCs) and radionuclide-drug conjugates (RDCs). Finally, we discuss the fundamentals behind drug conjugate-based anticancer therapeutics, along with their inherent advantages and associated challenges, as well as recent research advances. This review highlights the basic structures, coupling strategies, and development histories of five drug conjugates: ADCs, PDCs, SMDCs, APDCs, and RDCs. The mechanisms underlying drug conjugate-based anti-cancer therapies are discussed, along with their advantages, challenges, and recent research advancements.