Revolutionizing breast cancer treatment: the promise of antibody-drug conjugates.

Abstract

Antibody-drug conjugates (ADCs) have significantly advanced the treatment of breast cancer by integrating the specificity of monoclonal antibodies with the cytotoxic efficacy of chemotherapy, thereby enabling a targeted therapeutic approach that reduces off-target toxicity to normal tissues. Currently, 4 ADCs-sacituzumab govitecan, trastuzumab deruxtecan, trastuzumab emtansine, and the more-recent datopotamab deruxtecan-are approved for clinical application, with several others in advanced stages of development. Although these agents have demonstrated promising clinical efficacy, challenges such as ADC resistance and associated toxicities have emerged, underscoring the need for continued research. Multiple strategies are under investigation to enhance therapeutic benefit through combination regimens with other classes of medications, as are approaches to mitigate resistance mechanisms. Progress in next-generation ADCs, incorporating novel linkers and more potent cytotoxic payloads, holds promise for further improvement in clinical outcomes. Additionally, biomarker-driven strategies to identify those patients most likely to benefit from ADC therapy will support more personalized approaches to treatment. This review explores the structural and mechanistic features of ADCs in breast cancer, highlighting their therapeutic potential, and discusses ongoing clinical trials exploring new-generation ADCs and combination therapies.