Tyrosine kinase inhibitors (TKIs) represent a relatively large class of small-molecule inhibitors that compete with ATP for the catalytic binding site of tyrosine kinase proteins. While TKIs have demonstrated effectiveness in the treatment of multiple malignancies, including chronic myelogenous leukemia, gastrointestinal tumors, non-small cell lung cancers, and HER2-overexpressing breast cancers, as is almost always the case with anti-neoplastic agents, the development of resistance often imposes a limit on drug efficacy. One common survival response utilized by tumor cells to ensure their survival in response to different stressors, including anti-neoplastic drugs, is that of autophagy. The autophagic machinery in response to TKIs in multiple tumor models has largely been shown to be cytoprotective in nature, although there are a number of cases where autophagy has demonstrated a cytotoxic function. In this review, we provide an overview of the literature examining the role that autophagy plays in response to TKIs in different preclinical tumor model systems in an effort to determine whether autophagy suppression or modulation could be an effective adjuvant strategy to increase efficiency and/or overcome resistance to TKIs.
酪氨酸激酶抑制剂（TKIs）是一类数量较多的小分子抑制剂，它们通过与ATP竞争酪氨酸激酶蛋白的催化结合位点发挥作用。尽管TKIs在治疗多种恶性肿瘤（包括慢性髓性白血病、胃肠道肿瘤、非小细胞肺癌以及HER2过表达乳腺癌）中显示出疗效，但正如抗肿瘤药物几乎普遍面临的情况一样，耐药性的产生往往限制了药物疗效。肿瘤细胞为应对包括抗肿瘤药物在内的不同应激源而采用的常见生存反应之一是自噬。在多种肿瘤模型中，针对TKIs诱导的自噬机制大多被证明具有细胞保护作用，尽管也存在自噬发挥细胞毒性功能的案例。本综述通过梳理不同临床前肿瘤模型系统中自噬对TKIs反应的相关文献，旨在探讨抑制或调节自噬是否可能成为提高TKIs疗效和/或克服其耐药性的有效辅助策略。
Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?
肿瘤(癌症)患者之家