Reactive oxygen species and DNA damage response in cancer

Abstract

Compared with normal cells, cancer cells often have an increase in reactive oxygen species (ROS) level. This high level of ROS allows the activation of different pathways essential for cellular transformation and tumorigenesis development. Increase of ROS can be due to increase of production or decrease of detoxification, both situations being well described in various cancers. Oxidative stress is involved at every step of cancer development from the initiation to the metastasis. How ROS arise is still a matter of debates and may vary with tissues, cell types or other conditions and may happen following a large diversity of mechanisms. Both oncogenic and tumor suppressor mutations can lead to an increase of ROS. In this chapter, I review how ROS are produced and detoxified and how ROS can damage DNA leading to the genomic instability featured in cancers.

Keywords: Cancer; DNA damage; DNA repair; Genomic instability; Mutational signatures; Reactive oxygen species.