Epigenetic alterations in oesophageal carcinoma: The role of microRNAs in determination and prediction of chemo- and radiosensitivity in oesophageal cancer and its meaning for response control of neoadjuvant therapy

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Neoadjuvant treatment is nowadays a standard therapy for patients with locally advanced oesophageal carcinoma and improves the overall survival in those patients who respond to this therapeutic modality. But only about 40 % of patients respond to this preoperative treatment. Monitoring of the success of this treatment, which is currently based on histological, endoscopical and radiological assessments, is insufficient. Epigenetic changes have important roles in cancer development and treatment. In this context microRNAs have been shown to be useful biomarkers for classifying cancers and providing information about chemo- and radiosensitivity of various cancer types. Hence, the goal of this proposal is to investigate the role of microRNAs in prediction of chemo-/ radiosensitivity in oesophageal cancer and in the monitoring of the success of a neoadjuvant therapy in these patients. Therefore we use cell culture models and human pre- and posttherapeutic samples to determine the microRNA expression profiles before and after neoadjuvant therapy. Furthermore, we aim to identify likely target genes of the altered microRNAs. This will allow us to get a better insight into cellular processes which affect sensitivity to a neoadjuvant treatment. With these results we hope to provide a perspective for new diagnostic and therapeutic approaches that can affect neoadjuvant treatment in oesophageal cancer.