Targeted inhibition of DNA repair as strategy to tackle radiation resistance in head and neck cancers

Despite technological advances made in radiotherapy delivery, survival rate improved marginally over the last 30 years for head and neck cancer (HNSCC) patients. One of the reasons for the high local relapse is the DNA repair capacity of the irradiated cells, which can enable tumor cells to survive and provide a prominent mode of resistance and reduction in the therapeutic efficiency. Here, we propose to identify a subset of HNSCC patients that will be highly responsive to the combination of DNA repair inhibitors and radiotherapy and elucidate molecular mechanisms of the enhanced sensitivity. Next, we plan to validate our observations using HNSCC PDX models. Using UH Leuven HNSCC tumor bank, we will also optimize the detection of the identified biomarkers. The results of our study will lead to improved clinical trial designs for HNSCC patients and improved patient outcome on the long-term.