Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 6900 Lake Nona Blvd, Orlando, FL 32827, USA.
Int J Mol Sci. 2019 Dec 3;20(23):6094. doi: 10.3390/ijms20236094.
Relapsed disease following first-line therapy remains one of the central problems in cancer management, including chemotherapy, radiotherapy, growth factor receptor-based targeted therapy, and immune checkpoint-based immunotherapy. Cancer cells develop therapeutic resistance through both intrinsic and extrinsic mechanisms including cellular heterogeneity, drug tolerance, bypassing alternative signaling pathways, as well as the acquisition of new genetic mutations. Reactive oxygen species (ROSs) are byproducts originated from cellular oxidative metabolism. Recent discoveries have shown that a disabled antioxidant program leads to therapeutic resistance in several types of cancers. ROSs are finely tuned by dysregulated microRNAs, and vice versa. However, mechanisms of a crosstalk between ROSs and microRNAs in regulating therapeutic resistance are not clear. Here, we summarize how the microRNA-ROS network modulates cancer therapeutic tolerance and resistance and direct new vulnerable targets against drug tolerance and resistance for future applications.
一线治疗后复发疾病仍然是癌症管理的核心问题之一，包括化疗、放疗、基于生长因子受体的靶向治疗和基于免疫检查点的免疫治疗。癌细胞通过内在和外在机制产生治疗耐药性，包括细胞异质性、药物耐受性、绕过替代信号通路以及获得新的遗传突变。活性氧（ROS）是细胞氧化代谢产生的副产物。最近的发现表明，抗氧化剂程序的失灵会导致多种类型的癌症产生治疗耐药性。ROS 受到失调的 microRNAs 的精细调节，反之亦然。然而，ROS 和 microRNAs 之间相互作用调节治疗耐药性的机制尚不清楚。在这里，我们总结了 microRNA-ROS 网络如何调节癌症治疗耐受性和耐药性，并为未来的应用提供了针对药物耐受性和耐药性的新的脆弱靶点。
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