血液悪性腫瘍におけるADC耐性の解明：課題と新たなフロンティア

Antibody-drug conjugates (ADCs) initiated a pivotal therapeutic strategy in hematologic malignancies, by combining targeted cytotoxicity with high specificity and reduced systemic toxicity. However, despite promising clinical outcomes, resistance to ADCs raises a remarkable challenge, limiting their long-term efficacy. This review explored the multiplex mechanisms underlying ADC resistance emerging in different hematologic cancers, including overexpression of drug efflux pumps, antigen loss or downregulation, impaired intracellular trafficking, and altered apoptotic pathways. The review sheds the light on the role of tumor microenvironment in promoting resistance and hindering the ultimate ADCs efficacy as well as emerging strategies to overcome resistance such as combination therapies, next-generation ADCs, and biomarker-driven patient selection. Understanding the molecular basis of ADC resistance is crucial for optimizing treatment regimens and guiding future therapeutic development in hematologic malignancies.