Optimization of the preclinical assessment of DNA repair inhibitors in combination with radiotherapy in head and neck cancers

Head and neck cancers are the 7^th most frequent cancers worldwide, with yearly 2.500 new diagnoses in Belgium. In the majority of these cancers cytotoxic chemotherapy is combined with local radiotherapy. Still up to 50% of patients still die from local disease, indicating the urgent need for novel more selective treatment strategies. In the last decennia intensive effort has been put forward to find novel, more tumor/target specific therapies to answer the need of cancer patients. However, the progress in this field seems to be very slow and can be ascribed to a number of reasons but one important factor is the lack of rigorous design of preclinical studies in which the optimal scheduling and molecular interaction between different agents are studied. We propose to tackle these problems by thorough preclinical assessment of small molecular DNA repair inhibitors in combination with radiotherapy. More specific, we propose to assess the efficacy, optimal therapeutic scheme and molecular alterations of combination of DNA repair inhibitors with radiotherapy. The target selection is based on the knowledge that DNA repair inhibition can form an attractive strategy to improve radiotherapy, since DNA repair pathways can enable tumor cells to survive and reduce the therapeutic efficiency of radiotherapy.