Title: CRUK City of London Centre Radiation Research Unit
Funder: Cancer Research UK

Abstract: Radiotherapy is an extremely effective treatment for cancer, but it fails to cure the disease when we are unable to deliver a sufficient radiation dose to the target. This can be due to relative radiation resistance of the cancer, tumour heterogeneity or clonal evolution, metastatic spread, imprecise localisation or targeting of the tumour or a failure to achieve synergy with other anti-cancer treatments. Directly addressing these fundamental limitations has the potential to dramatically unlock the full potential of radiation-based cancer therapies. The CRUK City of London Centre proposes to form a Radiation Research Unit which brings together an extensive range of clinical facilities for advanced radiotherapy, the world’s largest Academic Health Science partnership, the UK’s largest and most diverse patient referral population and world leading cancer research and multi-disciplinary expertise across UCL Partners, Kings Health Partners and The Francis Crick Institute. The City of London Centre Radiation Research Unit will become a CRUK-wide focus for: Radiation resistance: To form a detailed mechanistic understanding of the roles of stem-like cancer cells, the tumour microenvironment and DNA damage and repair in clinical radiation resistance. Radiation combinations: To understand the effect of radiotherapy on the immune response in the context of the entire tumour microenvironment with a view to synergistic combination therapies. Targeting and technology: To match actual dose delivery of X-ray, proton or targeted radionuclides to the true potential of radiotherapy technology and to predict and measure the outcome using novel biomarkers in addition to RECIST and survival. These will be supported by, and feed into, two cross-cutting themes: Outcomes and risks: To build a comprehensive platform for radiotherapy data and apply artificial intelligence approaches to interrogate and predict clinical outcomes. Clinical translation: To establish a clinical trials platform, the Radnet Trials Hub, to ensure a strong forward and reverse translational element to every theme, with close involvement of PPI members experienced in radiotherapy trials. Our long term vision is to expand patient access to novel, radiation-based therapies, to implement novel radiotherapies, protocols and combinations throughout our partner hospitals and beyond, and to demonstrate improvements in patient outcomes and reduced side effects in radiotherapy patients, particularly in paediatric cases.

Lay abstract: Radiotherapy is an extremely effective treatment for cancer, but it fails to cure the disease when we are unable to deliver a sufficient radiation dose to the target. This can be due to relative radiation resistance of the cancer, tumour heterogeneity or clonal evolution, metastatic spread, imprecise localisation or targeting of the tumour or a failure to achieve synergy with other anti-cancer treatments. Directly addressing these fundamental limitations has the potential to dramatically unlock the full potential of radiation-based cancer therapies. The CRUK City of London Centre proposes to form a Radiation Research Unit which brings together an extensive range of clinical facilities for advanced radiotherapy, the world’s largest Academic Health Science partnership, the UK’s largest and most diverse patient referral population and world leading cancer research and multi-disciplinary expertise across UCL Partners, Kings Health Partners and The Francis Crick Institute. The City of London Centre Radiation Research Unit will become a CRUK-wide focus for: Radiation resistance: To form a detailed mechanistic understanding of the roles of stem-like cancer cells, the tumour microenvironment and DNA damage and repair in clinical radiation resistance. Radiation combinations: To understand the effect of radiotherapy on the immune response in the context of the entire tumour microenvironment with a view to synergistic combination therapies. Targeting and technology: To match actual dose delivery of X-ray, proton or targeted radionuclides to the true potential of radiotherapy technology and to predict and measure the outcome using novel biomarkers in addition to RECIST and survival. These will be supported by, and feed into, two cross-cutting themes: Outcomes and risks: To build a comprehensive platform for radiotherapy data and apply artificial intelligence approaches to interrogate and predict clinical outcomes. Clinical translation: To establish a clinical trials platform, the Radnet Trials Hub, to ensure a strong forward and reverse translational element to every theme, with close involvement of PPI members experienced in radiotherapy trials. Our long term vision is to expand patient access to novel, radiation-based therapies, to implement novel radiotherapies, protocols and combinations throughout our partner hospitals and beyond, and to demonstrate improvements in patient outcomes and reduced side effects in radiotherapy patients, particularly in paediatric cases.

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