Advances in therapeutic targeting of the DNA damage response in cancer

Abstract

The DNA damage response (DDR) is a series of pathways and processes required to repair lesions to DNA. These pathways range from repairing strand breaks to the double helix, damaged bases formed after oxidation or deamination, inaccurate DNA replication resulting in mispaired base alignment, intrastrand crosslinks that trigger cell death, and a plethora of other genomic insults. The DDR is believed to be a critical component of radio and chemoresistance in many cancers as well, with the tumor's ability to repair therapy induced damage being an important tool used to survive traditional chemotherapeutic agents. Here we summarize advances made in specifically targeting DDR proteins in cancer therapy and project on the potential breakthroughs and pitfalls to arise as the field progresses.