Targeting the DNA Damage Response in Cancer

DNA damage response in cancer is grouped into four functional groups such as DNA repair, DNA repair accessory functions, DNA damage signaling, and cell survival. Most cancer cells are expected to have proficient DNA repair pathways, such that therapeutic targeting of specific components of DNA repair pathways in cancer cells enhance the efficacy of anticancer treatments. Studies have found that cells induce extensive signal transduction pathways following induction of DNA damage that leads to the activation of cell cycle checkpoints and apoptosis depending on the cell type and the degree of damage. Cyclooxygenase-2 (COX-2) inhibitors, involved in the production of prostanoids, are found to promote DNA damage-induced cell killing of cancer cells. The combination of Chk1 inhibitions and radiation therapy is expected to be selectively toxic to p53-defective tumor cells.