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Director: Professor Amato Giaccia

Amato GiacciaThe current overall mission of the Medical Research Council Oxford Institute for Radiation Oncology (OIRO) is to explore aspects of radiation biology and physics that have direct applicability to the treatment of cancer underpinned by our understanding of how cells respond to and repair radiation induced damage and the impact of the microenvironment on radiation response. More specifically, the goals of the next QQR are to focus on “Increasing the therapeutic index for radiotherapy by exploiting DNA damage response inhibitors and chromatin modifications”. 

All of the MRC Investigators, MRC Junior Investigators and Affiliate Investigators in the programme will explore different aspects of the DNA damage response (DDR) and importantly in the context of the chromatin environment in which this occurs in order to increase the responsiveness of tumours to radiotherapy while at the same time reducing normal tissue damage. Together, an understanding of the biology of radiation-induced DNA damage in a physiologically relevant contextincluding the hypoxic microenvironment, and dynamic chromatin landscape will lead to a better understanding and improved patient outcomes. Most basic science research into DNA damage responses and the tumour microenvironment focus on DNA damage and hypoxia-mediated signal transduction and have focused on the major components of these pathways such as ATR, DNA-PK, and HIF, and while leading to translation into the clinic, have not delivered the new targets necessary to increase the translational pipeline for radiotherapy or mechanistic understanding of how the tumour microenvironment impacts the response to targeted therapies. The MRC Oxford Institute for Radiation Oncology has taken a unique, but also complementary approach to uncover new mechanistic understanding of tumour cell response to radiation and the microenvironment through focusing on chromatin changes and modifiers that could also yield a translational pipeline of new concepts for testing in clinical trials. The clinical trial infrastructure at Oxford, especially the Early Phase Clinical Trials Unit is one of the best in the UK at incorporating new molecular analysis and imaging technology that will aid us in translating our discoveries into early phase radiation oncology clinical trials. In addition, MRC OIRO benefits from the wealth of clinical radiation oncology experience that our colleagues in Oxford University Hospital brings us in attempting to increase the therapeutic index of radiation treatment.