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[Review] ROS and the DNA damage response in cancer. (Redox Biol, Dec 2018)

Srinivas US1, Tan BWQ1, Vellayappan BA2, Jeyasekharan AD3.

Author information
1Cancer Science Institute of Singapore, National University of Singapore, Singapore.
2Department of Radiation Oncology, National University Hospital, Singapore.
3Cancer Science Institute of Singapore, National University of Singapore, Singapore; Department of Haematology-Oncology, National University Hospital, Singapore. Electronic address: csiadj@nus.edu.sg.

Abstract
Reactive oxygen species (ROS) are a group of short-lived, highly reactive, oxygen-containing molecules that can induce DNA damage and affect the DNA damage response (DDR). There is unequivocal pre-clinical and clinical evidence that ROS influence the genotoxic stress caused by chemotherapeutics agents and ionizing radiation. Recent studies have provided mechanistic insight into how ROS can also influence the cellular response to DNA damage caused by genotoxic therapy, especially in the context of Double Strand Breaks (DSBs). This has led to the clinical evaluation of agents modulating ROS in combination with genotoxic therapy for cancer, with mixed success so far. These studies point to context dependent outcomes with ROS modulator combinations with Chemotherapy and radiotherapy, indicating a need for additional pre-clinical research in the field. In this review, we discuss the current knowledge on the effect of ROS in the DNA damage response, and its clinical relevance.

Keywords: Chemotherapy; DDR; DNA damage response; ROS; Radiotherapy; Reactive Oxygen Species

PMID: 30612957