Antibody–Drug Conjugates in Contemporary Oncology: A Clinical Perspective on Dose Optimization, Sequencing, and Combination Strategies

Abstract

Simple Summary Antibody–drug conjugates are cancer treatments designed to deliver potent cytotoxic drugs more selectively to tumor cells by linking a tumor-directed antibody to a therapeutic payload. This review examines the structural and biologic features that determine clinical activity, including target selection, linker stability, payload class, drug-to-antibody ratio, tumor penetration, biomarkers, toxicity, and resistance. Particular attention is given to the practical questions emerging as multiple ADCs enter the same malignancies and earlier treatment settings: how to select a biologically efficient dose, how to sequence agents with overlapping targets or payloads, and how to distinguish rational combinations from combinations that merely add toxicity. The next phase of ADC development will require not only improved molecular engineering, but also a more disciplined clinical framework for selecting, dosing, sequencing, and combining these agents.