Radiation therapy (RT) represents one of the most common and a valid therapeutic choices among cancer treatments, with almost 50% of all cancer patients receiving RT during the course of their disease. In the case of prostate cancer (PCa), RT shows an high efficiency both in curative and palliative intents. Ionizing radiations (IR) can determine DNA damages directly or indirectly, inducing the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), eventually causing cancer cell death. Different types of cancer cell death can occur after treatment with IR, from apoptosis to autophagy, depending on several factors including cell-intrinsic factors, radiation factors and microenvironmental factors. There is also evidence that IR are able to indirectly promote the activation of the immune system against the tumor, causing a form of cell death known as immunogenic cell death (ICD). Although RT exhibits high efficiency in the treatment of PCa, the onset of resistance to radiotherapy is not unusual and represents a serious problem to overcome. The enhancement of DNA repair capacity, with the overexpression of genes involved in DNA repair mechanisms, as well as the upregulation of antioxidant defenses, induced by continuative oxidative stress conditions, are two of the most common indicators of acquired resistance to RT. In addition, it has been documented in PCa the activation of the Epithelial-Mesenchymal Transition (EMT) program together with the expression of stemness properties as key role events in defining a radioresistant phenotype, even though the close connection between EMT and stemness and their relation with resistance to RT have not been clearly elucidate yet. Therefore the establishment of new model of disease could help in gaining a deepest comprehension of the mechanisms underlying radioresistance and unravel the intricate network between the different genes and molecular pathways involved in the acquisition of resistance to RT.
Radiation therapy represents one of the most common and valid therapeutic choices for patients with prostate cancer. Unfortunately the efficacy of RT is undermined by the possible development of tumor resistance mechanisms and, to date, the use of radiotherapy combinations with other types of treatments is necessary to obtain and consequently maintain an effective clinical control of the tumor. The analysis of the differences between radiosensitive and radioresistant tumor cell lines proposed in this study is implicitly based on the development of innovative in vitro models of disease, whose peculiarity lie in the fractionated scheme of irradiation used to establish the radioresistant lines, and will hopefully lead to a deeper knowledge of the unclear mechanisms underlying cancer resistance to radiotherapy. This project aims to move a first step towards a clearer understanding of radioresistance phenomena in prostate cancer to eventually gain an optimization of treatment combinations and a clear benefit for PCa patients.