Therapeutics Research Group, The University of Queensland Diamantina Institute, The University of Queensland, Translational Research Institute, Level 5 West, Brisbane, Australia.
School of Mathematical Sciences, Queensland University of Technology, Brisbane, Australia.
J Exp Clin Cancer Res. 2018 Nov 1;37(1):266. doi: 10.1186/s13046-018-0909-x.
Most chemotherapeutics elevate intracellular levels of reactive oxygen species (ROS), and many can alter redox-homeostasis of cancer cells. It is widely accepted that the anticancer effect of these chemotherapeutics is due to the induction of oxidative stress and ROS-mediated cell injury in cancer. However, various new therapeutic approaches targeting intracellular ROS levels have yielded mixed results. Since it is impossible to quantitatively detect dynamic ROS levels in tumors during and after chemotherapy in clinical settings, it is of increasing interest to apply mathematical modeling techniques to predict ROS levels for understanding complex tumor biology during chemotherapy. This review outlines the current understanding of the role of ROS in cancer cells during carcinogenesis and during chemotherapy, provides a critical analysis of the methods used for quantitative ROS detection and discusses the application of mathematical modeling in predicting treatment responses. Finally, we provide insights on and perspectives for future development of effective therapeutic ROS-inducing anticancer agents or antioxidants for cancer treatment.
大多数化疗药物会提高细胞内活性氧(ROS)的水平,并且许多药物可以改变癌细胞的氧化还原稳态。人们普遍认为,这些化疗药物的抗癌作用是由于诱导氧化应激和 ROS 介导的癌细胞损伤。然而,针对细胞内 ROS 水平的各种新的治疗方法的结果喜忧参半。由于在临床环境中不可能在化疗期间和之后定量检测肿瘤中的动态 ROS 水平,因此应用数学建模技术来预测 ROS 水平以了解化疗期间复杂的肿瘤生物学越来越受到关注。本综述概述了 ROS 在致癌作用和化疗过程中在癌细胞中的作用的现有认识,对定量 ROS 检测方法进行了批判性分析,并讨论了数学建模在预测治疗反应中的应用。最后,我们对有效诱导 ROS 的抗癌剂或抗氧化剂在癌症治疗中的未来发展提供了一些见解和展望。