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The generation of an isogenic model of radioresistance to study the role of microRNAs as biomarkers of response in oesophageal cancer

Niamh Lynam-Lennon, PhD Student
Niamh Lynam-Lennon, PhD Student

The standard treatment for oesophageal cancer employs a multimodal approach, whereby patients receive a course of chemotherapy and radiation therapy (CRT) to shrink their tumours and limit its spread to other sites, followed by surgery to remove the remaining tumour. Radiation therapy has played an important role in improving survival rates, however, tumour resistance to radiation remains a significant clinical problem. The elucidation of molecular mechanisms and markers of radioresistance would be of substantial benefit to cancer patients. We are working to identify biomarkers indicative of patient response to radiation therapy. This involves identifying genes and small non-coding RNA regulatory molecules, called microRNA, that are involved in the response to radiation and that play a role in conferring radioresistance to tumour cells. microRNAs are a relatively new discovery, and function to regulate genes within the cell. They play a vital role in important cellular processes such as cell survival and cell death, and mounting evidence also points to a role for these molecules in the response to radiation. We have developed a cell model of radioresistance in oesophageal adenocarcinoma and have identified several putative microRNA markers that are indicative of response to radiation. We are currently investigating the full functional role of these microRNA in radioresistance, and are assessing their potential as biomarkers of response to radiation, in both patient serum samples and tumour tissue samples from the departmental biobank. The data obtained in this project could ultimately be used in a diagnostic capacity to determine, prior to treatment, which patients are most likely to benefit from radiation therapy, facilitating individualisation of treatment. This work will also expand our knowledge of the critical mechanisms controlling tumour resistance to radiation therapy, and may identify novel molecular targets to enhance efficacy of radiation therapy.

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