DNA damage response and potential biomarkers of radiosensitivity in head and neck cancers: clinical implications

Abstract

Head and neck cancers include a wide variety of tumor sites that originate in the epithelium of the upper aerodigestive airways. The curative treatment of this group of pathologies most frequently involves multidisciplinary approach in which radiotherapy (RT) plays a central role. Treatment failures are mainly due to recurrences and local or regional evolution and rarely to distant metastases, which emphasizes the importance of ensuring local control. For patients with recurrences, the treatment options are significantly reduced, and prognosis is considerably attenuated. At the cellular level, the main irradiation target is the deoxyribonucleic acid (DNA), its lesions being largely responsible for radiation[1]induced cell death. However, not all DNA damage will have the same biological significance and a considerable part will be repaired through an intricate network of signaling proteins and repair pathways. Radiobiologically, compared to normal cells, tumor clonogens are defined by malfunction of DNA repair pathways. Tumors with an increased repair capacity, especially DNA double-strand breaks, the most lethal lesions induced by RT, will be radioresistant. The purpose of this review was to elucidate the mechanisms involved in avoiding radiation-induced apoptosis of head and neck cancers mediated by modulating the repair of DNA damage via p53, epidermal growth factor receptor (EGFR) and p16. The role of DNA damage-associated biomarkers in response to irradiation in clinical practice for the selection of personalized treatments and specifying the prognosis and, finally, the bases of immunotherapy association are presented.