Aberrations in DNA repair pathways in cancer and therapeutic significances.

Cancer cells show various types of mutations and aberrant expression in genes involved in DNA repair responses. These alterations induce genome instability and promote carcinogenesis steps and cancer progression processes. These defects in DNA repair have also been considered as suitable targets for cancer therapies; a most effective target so far clinically demonstrated is "homologous recombination repair defect" such as BRCA1/2 mutations, that were shown to cause synthetic lethality with inhibitors of poly(ADP-ribose) polymerase (PARP), which is involved in DNA repair as well as multiple physiological processes. Different approaches targeting genomic instability, including immune therapy targeting mismatch-repair deficiency, have also recently been demonstrated to be promising strategies. In these DNA repair targeting-strategies common issues could be how to optimize treatment and suppress/conquer the development of drug resistance. In this article, we review DNA repair response pathways and their alterations in cancer cells and impacts on therapeutic potentials for cancer treatments, including chemotherapy, radiation therapy and immune therapy.