The Effect of Radiotherapy on Head and Neck Cancer Cell Lines Following Exposure to Heat

Abstract

Fanconi anaemia (FA) is a rare, recessive, genetic disorder characterised by a predisposition to cancer. Patients with FA are 700 times more likely to develop head and neck squamouscell carcinomas including oral epithelial dysplasia (OED), a potentially malignant disorder of the oral mucosa. This increased likelihood suggests that the molecular mechanism responsible for dysplastic transformation may involve defects in the FA pathway. In this study, the significance of ataxia telangiectasia and Rad3-related protein (ATR), which is responsible for homologous recombination repair (HRR), was investigated. ATR protects against mutations in both normal squamous cells and cancer cells by inducing HRR, and thus is associated with radiotherapy resistance. This investigation was designed to study the effects of heat on DNA repair specific to the FA pathway. Western blotting was carried out to determine whether heat affects the ATR pathway, followed by survival assays to determine the viability of cells after heat treatment and then compared to cells treated with a specific ATR inhibitor. This project aims to discover whether heat could be used as a non-invasive treatment to increase the sensitivity of tumour cells towards radiotherapy leading to an improved treatment plan for patients suffering from head and neck cancers.