肿瘤细胞治疗研究
英文原题：Mechanisms of resistance to antibody-drug conjugates in cancers.
Mechanisms of resistance to antibody-drug conjugates in cancers.
近年来，随着分子靶向药物、单克隆抗体、免疫检查点抑制剂、双特异性抗体和CAR-T 细胞疗法等多种治疗模式的出现，癌症治疗取得了巨大进展。
近年来，随着分子靶向药物、单克隆抗体、免疫检查点抑制剂、双特异性抗体和CAR-T 细胞疗法等多种治疗模式的出现，癌症治疗取得了巨大进展。抗体药物偶联物（ADC）是癌症治疗的一项重要突破，部分ADC已获批用于多种类型的癌症。典型的ADC包括用于HER2阳性乳腺癌的trastuzumab emtansine、用于三阴性乳腺癌（TNBC）的sacituzumab govitecan，以及用于HER2阳性乳腺癌、胃癌和HER2突变阳性非小细胞肺癌的trastuzumab deruxtecan（T-DXd）。尽管这些药物已显示出治疗疗效，但几乎所有患者都会通过多种机制产生耐药性。在本文中，我们讨论了ADC耐药的主要机制，将其分为五类：与“靶抗原”相关的机制、“内化减少”、“溶酶体功能障碍”和“载荷敏感性”以及其他耐药机制[图1]。我们还讨论了克服ADC耐药的策略。
Cancer treatment has evolved dramatically in recent years with the advent of various modalities, including molecular-targeted drugs, monoclonal antibodies, immune checkpoint inhibitors, bispecific antibodies, and chimeric antigen receptor T-cell therapy. Antibody-drug conjugates (ADCs) represent an important breakthrough in cancer treatment, and some ADCs have been approved for use in several types of cancers. Typical ADCs include trastuzumab emtansine for HER2-positive breast cancer, sacituzumab govitecan for triple-negative breast cancer (TNBC), and trastuzumab deruxtecan (T-DXd) for HER2-positive breast cancer, gastric cancer, and HER2 mutation-positive non-small cell lung cancer. Although they have shown therapeutic efficacy, almost all patients develop resistance via multiple mechanisms. In this article, we discuss the major mechanisms of resistance to ADCs, classifying them into five categories: mechanisms related to 'target antigen,' 'decreased internalization,' 'lysosomal dysfunction,' and 'payload sensitivity' and other resistance mechanisms [Figure 1]. We also discuss the strategies for overcoming ADC resistance.
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