Ionizing radiation (IR) is a genuine genotoxic agent and a major modality in cancer treatment. IR disrupts DNA sequences and exerts mutagenic and/or cytotoxic properties that not only alter critical cellular functions but also impact tissues proximal and distal to the irradiated site. Unveiling the molecular events governing the diverse effects of IR at the cellular and organismal levels is relevant for both radiotherapy and radiation protection. Herein, we address changes in the expression of mammalian genes induced after the exposure of a wide range of tissues to various radiation types with distinct biophysical characteristics. First, we constructed a publicly available database, termed RadBioBase, which will be updated at regular intervals. RadBioBase includes comprehensive transcriptomes of mammalian cells across healthy and diseased tissues that respond to a range of radiation types and doses. Pertinent information was derived from a hybrid analysis based on stringent literature mining and transcriptomic studies. An integrative bioinformatics methodology, including functional enrichment analysis and machine learning techniques, was employed to unveil the characteristic biological pathways related to specific radiation types and their association with various diseases. We found that the effects of high linear energy transfer (LET) radiation on cell transcriptomes significantly differ from those caused by low LET and are consistent with immunomodulation, inflammation, oxidative stress responses and cell death. The transcriptome changes also depend on the dose since low doses up to 0.5 Gy are related with cytokine cascades, while higher doses with ROS metabolism. We additionally identified distinct gene signatures for different types of radiation. Overall, our data suggest that different radiation types and doses can trigger distinct trajectories of cell-intrinsic and cell-extrinsic pathways that hold promise to be manipulated toward improving radiotherapy efficiency and reducing systemic radiotoxicities.
Radiotherapy (RT) is a major part of cancer treatment. The reported variability in patient response to this modality can interfere with the continuation of best-possible care, promote side effects, and lead to long-term morbidity. Tools to predict a patient’s response to radiation could be highly useful in improving therapeutic outcomes while minimizing unnecessary and toxic exposure to radiation. This study investigates the potential of using molecular biomarkers as predictors of radiosensitivity in clinical practice. We review relative studies researching the positive correlation between various molecular biomarkers and patient radiosensitivity, including DNA damage response and repair proteins, inflammation and apoptosis markers, cell cycle regulators, and other biological markers. The clinical perspectives and applicability of these biomarkers in the prediction of radiosensitivity are also critically discussed. Conclusively, we underline the dynamics of molecular biomarkers to improve the efficacy and safety of radiotherapy in clinical practice and highlight the need for further research in this field. Identification of the most prominent markers is crucial for the personalization of therapies entailing ionizing radiation.
At the outbreak of the COVID-19 global crisis, diverse scientific groups suggested that this unprecedented emergency could act as a ‘blessing in disguise’