Radiotherapy alone or in combination with other anti-cancer treatments, such as chemotherapy and immunotherapy, is applied in half of all cancer patients, but despite all technical innovations approximately only 50% of the patients are cured. Radiotherapy efficacy is limited by 1) resistance mechanisms induced by the tumor and 2) adverse reactions in the co-irradiated surrounding normal tissues located in the path of the irradiation beam. Since technical improvements are reaching their limits, substantial improvements are now expected from biological insights on the mechanisms causing tumor cell resistance and normal tissue toxicities.
Our research program investigates in three scientific work packages the plasticity of an altered tumor metabolism and tumor microenvironment, including the immune system, prior to, and in response to radiotherapy, as well as related dose-limiting adverse effects in normal tissues.
Available dedicated precision image-guided small animal radiotherapy platforms, which require excellent imaging- and technology skills were used to investigate normal tissue- and tumor-oriented biological endpoints. Sparing normal tissue toxicity and the underlying biological mechanisms were further addressed by a novel type of irradiation applying high dose-rates (FLASH), i.e. deliver the radiotherapy dose in a split second, which only recently pointed towards a completely novel mechanism of ionizing radiation-induced cellular cytotoxicity. These endpoints have been investigated with photon-, electron- and in part with proton-radiotherapy, important to future treatment stratification from a biological perspective, and have exposed scientists to clinically relevant radiotherapy modalities.
The THERADNET network brought together 7 partners from different European academic institutions, and one non-academic partner, hosting 15 Early Stage Researchers (ESRs). The network also involved 10 associated partners, including industrial, oncology and patients’ advocacy organizations and publishers.
Scientific objectives: Altered tumor metabolism and immune responses were characterized at the preclinical level in tumor and normal tissue in response to irradiation. New targets have been identified and investigated for translation into clinically relevant treatment concepts.
Training objectives: State-of-the-art a) scientific training in applied radiobiology and b) training in transferable skill with a focus on digital communication.
European objectives: The number of researchers focusing on radiation biology is still very small in individual countries, so it is important to collaborate at the European level to achieve a critical mass of scientists with complementary expertise in cancer and radiation biology and to contribute to the formation of a young generation of researchers in this field of applied cancer research.
