Background/Objectives:ADCs bring an innovative strategy to cancer treatment by conjugating powerful cytotoxic agents to the specificity of monoclonal antibodies. This review discusses recent advancements and challenges in the field of ADCs, along with future potential applications.Methods:Studies focused on the development of ADCs were reviewed. These include the effects of payload improvements, linker technologies, antibody engineering, and ADC internalization, which were particular topics of examination regarding their role in pancreatic ductal adenocarcinoma (PDAC) and triple-negative breast cancer (TNBC). The efficacy of some ADCs for pancreatic and breast cancers was compared.Results:In TNBC, ADCs such as sacituzumab govitecan and trastuzumab deruxtecan have improved progression-free survival in advanced cases. In contrast, PDAC ADC development is challenged by low antigen density and poor internalization; despite evidence of target engagement in early trials targeting mesothelin and MUC1, ADCs for PDAC have yet to achieve significant clinical efficacy or regulatory approval.Conclusions:While ADCs have significantly advanced treatment options in TNBC, PDAC remains a difficult target due to its stroma-rich microenvironment and lack of high-density, tumor-specific antigens. This article emphasizes the need for tailor-made ADC designs to enhance results in various types of cancers and provides valuable insight into future advancements in precision oncology.
背景/目的：抗体药物偶联物（ADCs）通过将强效细胞毒性药物与单克隆抗体的特异性相结合，为癌症治疗带来了创新策略。本综述探讨了ADCs领域的最新进展与挑战，并展望其未来潜在应用。 方法：本文回顾了聚焦于ADCs开发的相关研究，重点考察了有效载荷优化、连接子技术、抗体工程及ADC内吞作用等方面，并特别分析了这些因素在胰腺导管腺癌（PDAC）和三阴性乳腺癌（TNBC）治疗中的作用。研究比较了部分ADCs在胰腺癌和乳腺癌中的疗效差异。 结果：在TNBC治疗中，戈沙妥珠单抗与德曲妥珠单抗等ADCs已能改善晚期患者的无进展生存期。相比之下，PDAC的ADC研发因抗原密度低、内吞效率差而面临挑战；尽管早期针对间皮素和MUC1的临床试验已证实靶点结合，但针对PDAC的ADCs尚未取得显著临床疗效或获得监管批准。 结论：虽然ADCs显著拓展了TNBC的治疗选择，但PDAC因其富含基质的微环境及缺乏高密度肿瘤特异性抗原，仍是难以攻克的治疗靶点。本文强调需通过定制化ADC设计以提升各类癌症的治疗效果，并为精准肿瘤学的未来发展提供了重要见解。
Advancing Antibody–Drug Conjugates: Precision Oncology Approaches for Breast and Pancreatic Cancers
肿瘤(癌症)患者之家