Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Trends Cancer. 2023 Apr;9(4):339-354. doi: 10.1016/j.trecan.2023.01.003. Epub 2023 Feb 4.
Antibody-drug conjugates (ADCs) have become a credentialled class of anticancer drugs for both solid and hematological malignancies, with regulatory approvals mainly as single agents. Despite extensive preclinical and clinical efforts to develop rational ADC-based combinations, to date only a limited number have demonstrated survival improvements over standard of care. The most appealing partners for ADCs are those that offer additive or synergistic effects on tumor cells or their microenvironment without unacceptable overlapping toxicities. Coadministration with antiangiogenic compounds, HER2-targeting drugs, DNA-damage response agents and immune checkpoint inhibitors (ICIs) represent active forerunners. Through the identification of targets with tumor-specific expression, improved conjugation technologies, and novel linkers and payloads offering superior therapeutic indices, the next generation of ADCs brings optimism to combinatorial approaches.
抗体偶联药物 (ADCs) 已成为治疗实体瘤和血液系统恶性肿瘤的一类有资质的抗癌药物，主要作为单一药物获得监管批准。尽管在开发合理的 ADC 联合治疗方面进行了广泛的临床前和临床研究，但迄今为止，只有少数药物在标准治疗的基础上显示出了生存改善。与 ADC 最具吸引力的联合治疗药物是那些对肿瘤细胞或其微环境具有相加或协同作用，而没有不可接受的重叠毒性的药物。与抗血管生成药物、HER2 靶向药物、DNA 损伤反应药物和免疫检查点抑制剂 (ICI) 的联合应用是目前的研究热点。通过鉴定具有肿瘤特异性表达的靶点、改进的偶联技术，以及具有更好治疗指数的新型连接子和有效载荷，下一代 ADC 为联合治疗方法带来了乐观前景。
