UKHSA project - Identifying biomarkers to prevent medical radiation toxicity: Role of Adipose tissue in skin toxicity during radiotherapy
UKHSA Supervisors: Christophe Badie (UKHSA), Lourdes Cruz Garcia
Dept Oncology Supervisors: Dr Ejung Moon, Dr Mark Hill
Project Overview
This is a funded project, with a studentship package covering Home (UK) status fees. Radiotherapy is a common treatment to reduce the risk of numerous types of cancers expanding or coming back. However, the effects of radiotherapy are not specific to tumour cells and may produce toxicity due to exposure of surrounding organs and tissues.
Breast cancer is the most common cancer in the UK and radiation therapy is often given after surgery. After the treatment, skin toxicity is a frequent side effect affecting 70%-100% of patients for a long-time post-treatment, therefore leading to interruption of treatment and decreasing their long-term quality of life. Reactions occur within 1–4 weeks of treatment and range from erythema to dry or wet desquamation. Importantly, there is currently, no reliable method for determining treatment risk caused by radiotherapy.
During radiotherapy, due to the composition of the breast (90% fat tissue), high percentage of adipose tissue is inevitable exposed to radiation. Adipose tissue has high radiation sensitivity and presents a strong inflammatory response to radiation. Dysregulation and inflammation of adipose tissue due to irradiation is associated with cutaneous toxicity. Hence, we hypothesis that adipose tissue strongly contributes to radiation-induced skin toxicity and adipose-associated gene and protein markers can be detected in skin biopsies and blood to predict radiation sensitivity in radiotherapy patients.
Therefore, this DPhil proposal aims to investigate the implications of adipose tissue on the development of skin toxicity during radiotherapy. This proposal will study the response of adipose tissue to radiation and will evaluate the impact of communication between adipose tissue and skin on inducing skin damage aiming to identify potential biomarkers to predict development of skin toxicity after radiation exposure.
This research will provide new tools to predict the outcomes of radiotherapy to be able to personalize treatments and prevent adverse effects.
Training Opportunities
We will provide training in molecular biology techniques (RNA extraction, PCR, qPCR) together with cell culture, Elisa, western blot, nanopore library preparation, sequencing using a GridION/P2S sequencer and bioinformatic analysis. The project will require use of different skin models, MTT assay and permeability tests, Elisa immunoassays for specific adipokines, Human Adipokine Antibody Array and use of Olink technology for proteomic analysis.
References
Meng G, Tang X, Yang Z, Benesch MGK, Marshall A, Murray D, et al. Implications for breast cancer treatment from increased autotaxin production in adipose tissue after radiotherapy. FASEB J. 2017;31(9):4064-77.
Cruz-Garcia L, O'Brien G, Sipos B, Mayes S, Love MI, Turner DJ, et al. Generation of a Transcriptional Radiation Exposure Signature in Human Blood Using Long-Read Nanopore Sequencing. Radiat Res. 2020;193(2):143-54.
Silberg J, Nowak K, Larose M, Wright C, Simone NL. Effect of elevated BMI on radiation toxicity in early stage breast cancer patients. 2016;34(15_suppl):1049-.