Membrane receptor signaling and control of DNA repair after exposure to ionizing radiation

Abstract

Accumulated evidence indicates that activation of erbB family of receptors, when mutated or over-expressed, mediates chemo- and radiotherapy resistance. In this context signaling pathways down-stream of epidermal growth factor receptor (EGFR), when abnormally activated, invoke cell survival mechanisms, which leads to resistance against radiation. In several reports it has been demonstrated that molecular targeting of EGFR signaling enhances the cytotoxic effects of radiotherapy. The radiosensitizing effects of EGFR antagonists correlate with a suppression of the ability of tumor cells to repair radiation-induced DNA double strand breaks (DNA-DSBs) through non-homologous end-joining repair pathway (NHEJ). The purpose of this review is to highlight the function of EGFR and erbB2 receptors on signaling pathways, i. e. PI3K/Akt activated by ionizing radiation (IR) and involved in repair of DNA-DSB which can explain the radiosensitizing effects of related antagonists. Advances in understanding the mechanism of erbB-signaling in regulating DNA-DSB repair will promote translational approaches to test new strategies for clinically applicable molecular targeting.