Molecular mechanisms of ROS-modulated cancer chemoresistance and therapeutic strategies.

Drug resistance is the main obstacle to achieving a cure in many cancer patients. Reactive oxygen species (ROS) are master regulators of cancer development that act through complex mechanisms. Remarkably, ROS levels and antioxidant content are typically higher in drug-resistant cancer cells than in non-resistant and normal cells, and have been shown to play a central role in modulating drug resistance. Therefore, determining the underlying functions of ROS in the modulation of drug resistance will contribute to develop therapies that sensitize cancer resistant cells by leveraging ROS modulation. In this review, we summarize the notable literature on the sources and regulation of ROS production and highlight the complex roles of ROS in cancer chemoresistance, encompassing transcription factor–mediated chemoresistance, maintenance of cancer stem cells, and their impact on the tumor microenvironment. We also discuss the potential of ROS-targeted therapies in overcoming tumor therapeutic resistance. [Display omitted] • Redox regulation in tumor cells participated in the promotion of chemoresistance. • Many clinical trials targeting ROS modulators are ongoing, mostly phase I or II. • ROS modulates chemoresistance of tumor by impacting TFs, CSCs and TME. [ABSTRACT FROM AUTHOR]