Antibody-drug conjugates in recurrent or metastatic HNSCC: relevant targets, clinical development, and future prospects

Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a highly aggressive disease entity with poor prognosis. Current systemic treatment regimens, including chemotherapy, targeted therapy, and immune checkpoint inhibitors, provide only limited and often short-lived clinical benefits. As an innovative therapeutic approach, antibody-drug conjugates (ADCs) combine the tumor-targeting specificity of monoclonal antibodies with the potent cytotoxicity of the conjugated payload, enabling selective delivery of highly active drugs to cancer cells. Given the urgent need to improve clinical outcomes for R/M HNSCC, ADCs have emerged as a highly promising therapeutic strategy and are increasingly becoming the focus of translational research and clinical trials, with encouraging signals observed in both early and late-stage trials. This review comprehensively outlines the biological principles, antigen targets, and current clinical development progress of ADCs in treating R/M HNSCC. It begins with a brief explanation of ADC structural principles, followed by a systematic summary of all preclinical and clinical evidence supporting ADC therapy.