Antibody-Drug Conjugates Reshape the Landscape of Cancer Therapy: Evolution, Challenges and Future Perspectives from the Concept of "Magic Bullet" to Clinical Application.

purpose of reviewAntibody-drug conjugates (ADCs), generated by covalently linking tumor-targeted monoclonal antibodies to highly potent cytotoxic payloads, have emerged as a pivotal strategy for precision cytotoxic therapy in oncology. Focused on the central theme that technological iteration drives paradigm shifts in cancer treatment, this review systematically summarizes the historical development, clinical applications, current challenges, and future perspectives of ADCs. RECENT

findingsADCs have evolved through three generations of technological advances. They have reshaped the treatment landscape across multiple malignancies, advancing from late-line salvage therapy to first-line standard treatment and neoadjuvant settings, and have also begun to show promise in pan-targeted therapy. However, drug resistance and severe adverse events remain key challenges. Next-generation ADC candidates, optimized combination strategies, and the integration of artificial intelligence are being explored to overcome these limitations. ADCs represent a transformative therapeutic modality with demonstrated efficacy across diverse tumor types and treatment lines. While challenges persist, ongoing innovations hold promise for enhancing their clinical utility through precise target selection, optimized payload delivery, and intelligent therapeutic design.