New insights into the cellular response to complex DNA damage induced by proton beam therapy

点击翻译按钮获取中文摘要

Radiotherapy is still the most effective treatment for a number of human cancers, and the emergence of proton beam therapy (PBT) facilities in the UK, particularly in Manchester and London (operational from late 2018 and 2021, respectively), is likely to signal a new era for cancer treatment. This is due to the fact that PBT is a precision technique able to deliver the majority of the radiation dose directly to the cancer, thus sparing the surrounding normal tissues of any unwanted dose of radiation and reducing the adverse side-effects that are commonly observed with conventional radiotherapy. However whilst radiotherapy, including PBT, is known to act by causing damage to the DNA of cancer cells causing them to die, there is still not a complete understanding of the mechanisms which the cells use to repair certain types of DNA damage and that can cause significant resistance to treatment.This proposal therefore aims to reveal new knowledge into the basic biological mechanisms that cancer cells use to repair DNA damage caused by PBT, with the future goal of providing leads to the development of new strategies in combination with PBT for effective cancer treatment. Indeed, this study will largely employ cells derived from patients with head and neck cancer, which is a priority tumour research area within the University of Liverpool due to the high local incidence, but also a tumour which is increasingly being treated with PBT worldwide. Therefore, this proposal has the significant potential to devise future optimal treatments using PBT for head and neck cancer patients, leading to reductions in adverse side-effects and improvement in quality of life, but more importantly to increases in overall survival rates.