Title: RadNet-Cambridge - exploiting biology for radiation research translation into patient benefit
Funder: Cancer Research UK

Abstract: Background Radiotherapy is a mainstay of cancer treatment, but we still do not understand completely why some patients respond well and others do not. Further research is needed to understand the biology of radiosensitivity/radioresistance and exploit this knowledge to improve patient outcomes. Aims The long-term objective is to increase survival and optimise quality-of-life of all patients requiring radiotherapy. We will implement this via four shorter-term objectives: • Develop a critical mass of internationally leading, biologically-driven discovery and translational radiation research across five themes and three tumour sites - breast, brain (including paediatrics) and lung cancer • Develop cutting-edge research infrastructure and capability to deliver innovative radiation research • Build a translational radiation research pipeline, with opportunity for reverse translation • Train and support the radiation researchers of the future Methods We will develop five interlinked workstreams: 1. Understanding cell biology of radiation-induced DNA damage response (DDR) to exploit/counteract radioresistance 2. Developing genetic approaches to defining drug-radiation combinations 3. Developing and interrogating clinically relevant small animal tumour models to identify and robustly test novel radiotherapy strategies 4. Designing translation-rich novel neo-adjuvant radiotherapy and biomarker-driven clinical trials 5. Integrating radiogenomics, radiomics and Artificial Intelligence to interrogate tumour/normal tissue outcomes following radiotherapy We will build upon existing CRUK Cambridge Major Centre infrastructure, where academia and industry already connect to enable world-class collaboration. The first two workstreams introduce new radiation research themes in collaboration with world-leading scientific groups (Jackson – DDR; Hannon – Functional genomics), realised through recruitment of two new Junior Group Leaders. Pre-clinical radiation models will mirror clinical treatment allowing seamless progression into clinical trials. Radiotherapy clinical trials will facilitate serial bio-sampling to develop co-clinical animal trials for reverse translation. How the results of this research will be used Our pre-clinical workstreams will provide a pipeline of radiation research facilitating development of highly focused biologically-driven radiation clinical trials that translate into clinical practice for appropriately selected patients. Workstreams 4 will support provision of serial bio-samples to develop/validate biomarkers and workstream 5 will use Artificial Intelligence to incorporate radiomics and genomics to produce a truly integrative radiation research resource. This process is designed to produce focused, high-quality and impactful radiation research to accelerate new practice into the clinic for patient benefit, particularly those with cancers of unmet need. We will continue to collaborate with other RadNet centres to create a network of highly integrated radiation research to ultimately improve survival and minimise toxicity.

Lay abstract: Background Radiotherapy is a mainstay of cancer treatment, but we still do not understand completely why some patients respond well and others do not. Further research is needed to understand the biology of radiosensitivity/radioresistance and exploit this knowledge to improve patient outcomes. Aims The long-term objective is to increase survival and optimise quality-of-life of all patients requiring radiotherapy. We will implement this via four shorter-term objectives: • Develop a critical mass of internationally leading, biologically-driven discovery and translational radiation research across five themes and three tumour sites - breast, brain (including paediatrics) and lung cancer • Develop cutting-edge research infrastructure and capability to deliver innovative radiation research • Build a translational radiation research pipeline, with opportunity for reverse translation • Train and support the radiation researchers of the future Methods We will develop five interlinked workstreams: 1. Understanding cell biology of radiation-induced DNA damage response (DDR) to exploit/counteract radioresistance 2. Developing genetic approaches to defining drug-radiation combinations 3. Developing and interrogating clinically relevant small animal tumour models to identify and robustly test novel radiotherapy strategies 4. Designing translation-rich novel neo-adjuvant radiotherapy and biomarker-driven clinical trials 5. Integrating radiogenomics, radiomics and Artificial Intelligence to interrogate tumour/normal tissue outcomes following radiotherapy We will build upon existing CRUK Cambridge Major Centre infrastructure, where academia and industry already connect to enable world-class collaboration. The first two workstreams introduce new radiation research themes in collaboration with world-leading scientific groups (Jackson – DDR; Hannon – Functional genomics), realised through recruitment of two new Junior Group Leaders. Pre-clinical radiation models will mirror clinical treatment allowing seamless progression into clinical trials. Radiotherapy clinical trials will facilitate serial bio-sampling to develop co-clinical animal trials for reverse translation. How the results of this research will be used Our pre-clinical workstreams will provide a pipeline of radiation research facilitating development of highly focused biologically-driven radiation clinical trials that translate into clinical practice for appropriately selected patients. Workstreams 4 will support provision of serial bio-samples to develop/validate biomarkers and workstream 5 will use Artificial Intelligence to incorporate radiomics and genomics to produce a truly integrative radiation research resource. This process is designed to produce focused, high-quality and impactful radiation research to accelerate new practice into the clinic for patient benefit, particularly those with cancers of unmet need. We will continue to collaborate with other RadNet centres to create a network of highly integrated radiation research to ultimately improve survival and minimise toxicity.

Research activity codes: 5.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS