Molecular determinants of radiosensitivity in normal and tumor tissue: A bioinformatic approach

Abstract Although radiation therapy is a treatment of choice for cancer, a high percentage of patients develop adverse effects in normal tissue following radiotherapy, mainly, due to genetic factors. Notably, although it is established that a lower dose of ionizing radiation can minimize the tumor cell population in radiosensitive cancer patients, the sensitivity of tumor cells to radiation has not gained enough attention. In this mini-review, the molecular pathways/mechanisms and the related molecules involved in clinically relevant radiotoxicity, as well as normal and tumor cell radiosensitivity, were investigated for various types of cancers employing bioinformatics approaches. A total of 255 genes/gene products were retrieved and investigated in this study, which are implicated in pathways related mainly to DNA damage repair, oxidative stress, apoptosis and fibrosis. Furthermore, a novel molecular gene signature of normal tissue radiotoxicity was identified. The findings of our study could be utilized by healthcare professionals in personalized clinical decision-making, in order to efficiently sensitize tumor cells to radiation and yet minimize adverse effects in the adjacent normal tissues as well as to improve the quality of life in cancer patients undergoing radiotherapy.