Targeting base excision repair as a sensitization strategy in radiotherapy

Abstract

Cellular DNA repair determines survival after ionizing radiation. Human tumors commonly exhibit aberrant DNA repair since they drive mutagenesis and chromosomal instability. Recent reports have shown alterations in the base excision repair (BER) and single strand break repair (SSBR) pathways in human tumors. Here we review these reports with respect to radiation sensitivity and the attempts to target such tumor-specific BER/SSBR aberrations. These aberrations can alter cellular resistance to therapeutic agents, including radiation. Some strategies therefore aim to counteract the radioresistance mediated by such aberrant DNA repair. Other strategies aim to exploit the dependence of the tumor, but not the normal cells, on backup repair mechanisms after radiation, therefore increasing the therapeutic window. Such tumor-targeted radiosensitization holds promise for increasing the efficacy of radiotherapy.