Antibody–Drug Conjugates in Breast Cancer: Navigating Innovations, Overcoming Resistance, and Shaping Future Therapies
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MDPI
Abstract
Antibody–drug conjugates (ADCs) have revolutionized breast cancer (BC) therapy by combining
targeted antibody specificity with potent cytotoxic payloads, thereby enhancing efficacy while
minimizing systemic toxicity. This review highlights significant innovations driving ADC
development alongside persistent challenges. Recent advancements include novel antibody–
drug conjugate (ADC) designs targeting diverse antigens, such as HER2, HER3, and CD276,
demonstrating potent anti-tumor activity and improved strategies for drug delivery. For
instance, dual-payload ADCs and those leveraging extracellular vesicles offer new dimensions
in precision oncology. The integration of ADCs into sequential therapy, such as sacituzumab
govitecan with TOP1/PARP inhibitors, further underscores their synergistic potential. Despite
these innovations, critical challenges remain, including tumor heterogeneity and acquired drug
resistance, which often involve complex molecular alterations. Moreover, optimizing ADC
components, including linker chemistry and payload characteristics, is essential for ensuring
stability and minimizing off-target toxicity. The burgeoning role of artificial intelligence and
machine learning is pivotal in accelerating the design of ADCs, target identification, and
personalized patient stratification. This review aims to comprehensively explore the cuttingedge
innovations and inherent challenges in ADC development for BC, providing a holistic
perspective on their current impact and future trajectory.
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Except where otherwise noted, this item's license is described as Attribution 4.0 International