Antibody-drug Conjugates in Oncology: A Comprehensive Review of Mechanism, Efficacy, and Toxicity Management

Abstract

Antibody-drug conjugates (ADCs) represent a transformative advancement in oncology, offering targeted delivery of cytotoxic agents to malignant cells while minimizing damage to healthy tissues; however, their complex mechanism, variable efficacy, and unique toxicity profiles necessitate a comprehensive review to guide clinical practice and future research. This review systematically examines the mechanism of action of ADCs, including antibody specificity, linker stability, and payload potency, evaluates their clinical efficacy across various malignancies such as breast, lung, and gynecologic cancers, and discusses evidence-based strategies for managing ADC-associated toxicities, including hematologic, neurologic, and ocular adverse events. Furthermore, it explores current challenges such as drug resistance and off-target effects, and highlights emerging approaches to optimize ADC design, including novel linkers, payloads, and combination therapies. Future directions emphasize the integration of predictive biomarkers, personalized dosing strategies, and the development of next-generation ADCs to enhance therapeutic precision and improve patient outcomes in oncology.