PDF(Pubmed)
Abstract：
BACKGROUND: In tumor treatment, protein tyrosine kinase inhibitors (TKIs) have been extensively utilized. However, the efficacy of TKI is significantly compromised by drug resistance. Consequently, finding an effective solution to overcome TKI resistance becomes crucial. Reactive oxygen species (ROS) are a group of highly active molecules that play important roles in targeted cancer therapy including TKI targeted therapy. In this review, we concentrate on the ROS-associated mechanisms of TKI lethality in tumors and strategies for regulating ROS to reverse TKI resistance in cancer.
METHODS: Elevated ROS levels often manifest during TKI therapy in cancers, potentially causing organelle damage and cell death, which are critical to the success of TKIs in eradicating cancer cells. However, it is noteworthy that cancer cells might initiate resistance pathways to shield themselves from ROS-induced damage, leading to TKI resistance. Addressing this challenge involves blocking these resistance pathways, for instance, the NRF2-KEAP1 axis and protective autophagy, to promote ROS accumulation in cells, thereby resensitizing drug-resistant cancer cells to TKIs. Additional effective approaches inducing ROS generation within drug-resistant cells and providing exogenous ROS stimulation.
CONCLUSIONS: ROS play pivotal roles in the eradication of tumor cells by TKI. Harnessing the accumulation of ROS to overcome TKI resistance is an effective and widely applicable approach.
METHODS: Elevated ROS levels often manifest during TKI therapy in cancers, potentially causing organelle damage and cell death, which are critical to the success of TKIs in eradicating cancer cells. However, it is noteworthy that cancer cells might initiate resistance pathways to shield themselves from ROS-induced damage, leading to TKI resistance. Addressing this challenge involves blocking these resistance pathways, for instance, the NRF2-KEAP1 axis and protective autophagy, to promote ROS accumulation in cells, thereby resensitizing drug-resistant cancer cells to TKIs. Additional effective approaches inducing ROS generation within drug-resistant cells and providing exogenous ROS stimulation.
CONCLUSIONS: ROS play pivotal roles in the eradication of tumor cells by TKI. Harnessing the accumulation of ROS to overcome TKI resistance is an effective and widely applicable approach.
摘要：
背景：在肿瘤治疗中，蛋白酪氨酸激酶抑制剂(TKIs)已被广泛使用。然而,TKI的疗效明显受到耐药性的影响。因此,找到克服TKI耐药性的有效解决方案变得至关重要。活性氧（ROS）是一组高活性分子，在包括TKI靶向治疗在内的靶向癌症治疗中起重要作用。在这次审查中,我们专注于肿瘤中TKI致死率的ROS相关机制以及调节ROS逆转肿瘤中TKI耐药的策略。
方法：在癌症的TKI治疗过程中，经常表现出ROS水平升高，可能导致细胞器损伤和细胞死亡，这对TKIs成功根除癌细胞至关重要。然而,值得注意的是，癌细胞可能会启动抵抗途径来保护自己免受ROS诱导的损害，导致TKI抵抗。应对这一挑战涉及阻断这些抗性途径，例如,NRF2-KEAP1轴和保护性自噬，促进ROS在细胞中的积累，从而使耐药癌细胞对TKIs重新敏感。诱导耐药细胞内ROS产生并提供外源性ROS刺激的其他有效方法。
结论：ROS在TKI根除肿瘤细胞中起关键作用。利用ROS的积累来克服TKI抗性是一种有效且广泛适用的方法。
方法：在癌症的TKI治疗过程中，经常表现出ROS水平升高，可能导致细胞器损伤和细胞死亡，这对TKIs成功根除癌细胞至关重要。然而,值得注意的是，癌细胞可能会启动抵抗途径来保护自己免受ROS诱导的损害，导致TKI抵抗。应对这一挑战涉及阻断这些抗性途径，例如,NRF2-KEAP1轴和保护性自噬，促进ROS在细胞中的积累，从而使耐药癌细胞对TKIs重新敏感。诱导耐药细胞内ROS产生并提供外源性ROS刺激的其他有效方法。
结论：ROS在TKI根除肿瘤细胞中起关键作用。利用ROS的积累来克服TKI抗性是一种有效且广泛适用的方法。
