Hypoxia is a common feature of human solid tumors and is considered as one main biological factor promoting tumor cell resistance to radiotherapy. Others and we revealed that chronic intermittent hypoxia acts as an important driver of adaptive changes that allow the cancer cells to survive these highly adverse conditions and promote tumor heterogeneity. A hypoxia/reoxygenation-induced metabolic reprogramming allowed the cancer cells to meet their bioenergetic and metabolic demands for sustained proliferation and survival after exposure to ionizing radiation. But the contribution of the genetic background to the metabolic response to radiotherapy and of the tumor cell intrinsic or induced metabolic plasticity to the escape of the cancer cells from radiotherapy remain to be defined.
The proposed project will profile metabolic demands of cancer cells with distinct genetic backgrounds upon exposure to ionizing radiation under diverse environmental conditions. Novel therapeutic strategies for overcoming intrinsic and acquired mechanisms for metabolic escape from radiotherapy will be defined and marker constellations for individualization of cancer radiotherapy will be predicted and validated in vitro and in vivo.