DNA Repair: Translation to the Clinic

Abstract

It has been well established that an accumulation of mutations in DNA, whether caused by external sources (e.g. ultraviolet light, radioactivity) or internal sources (e.g. metabolic by-products, such as reactive oxygen species), has the potential to cause a cell to undergo carcinogenesis and increase the risk for the development of cancer. Therefore, it is critically important for a cell to have the capacity to properly respond to and repair DNA damage as it occurs. The DNA damage response (DDR) describes a collection of DNA repair pathways that aid in the protection of genomic integrity by detecting myriad types of DNA damage and initiating the correct DNA repair pathway. In many instances, a deficiency in the DDR, whether inherited or spontaneously assumed, can increase the risk of carcinogenesis and ultimately tumorigenesis through the accumulation of mutations that fail to be properly repaired. Interestingly, although disruption of the DDR can lead to the initial genomic instability that can ultimately cause carcinogenesis, the DDR has also proven to be an invaluable target for anticancer drugs and therapies. Making matters more complicated, the DDR is also involved in the resistance to first-line cancer therapy. In this review, we will consider therapies already in use in the clinic and ongoing research into other avenues of treatment that target DNA repair pathways in cancer.