Identification of new inhibitors of DNA-damage repair for cancer treatment
Radiotherapy is widely used in cancer treatment. Cancer cell killing is largely obtained through the induction of DNA breaks by ionizing radiation. However, human cells are equipped with a repair machinery that may counteract the damage caused by radiation and help the cancer cells survive. Therefore, one way to increase the efficiency of radiotherapy would be to inhibit these repair mechanisms. Indeed, several inhibitors interfering with DNA-damage repair have either been approved or are explored in clinical trials for cancer treatment. However, the discovery of new and/or more efficient inhibitors is still needed.
The aim of this project is to identify new druggable targets of radiation induced DNA-damage repair. We have recently performed flow cytometry based screens in cancer cell lines treated with radiation and drug libraries, where we have identified several candidate drugs inhibiting the repair of DNA-damage caused by radiation. The student will validate the effect of one or more of these drugs, and investigate whether the reduced repair capacity is associated with reduced survival. Furthermore, the student will explore the mechanistic details of how these drugs work to inhibit repair and increase cell killing. Because cancer is not one but many different diseases that respond to treatment in different ways, it is important to understand the mechanistic details behind drug/radiation combinations, in order to make good treatment decisions in the future.
The student will learn how to use various methods to explore DNA-damage signaling and cell death in response to ionizing radiation. Among these methods are: DNA-damage induction by the use of an X-ray machine, multiparameter flow cytometry, western blotting and immunofluorescence microscopy to detect signaling events, and clonogenic survival and metabolic assays to study cell viability. More screens may be initiated, and in that event the student will get experience in how to use automated equipment for large scale experiments.
We seek a highly motivated and dedicated student with interest in molecular cancer research.
Group Leader Randi G. Syljuåsen
Scientist Gro Elise Rødland
Radiation Biology and DNA damage signaling
Department of Radiation Biology
Institute for Cancer Research
Norwegian Radium Hospital
Oslo University Hospital