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

新辅助治疗是目前局部晚期食管癌患者的标准治疗方法，并提高了对这种治疗方式有反应的患者的总生存率。但只有大约40%的患者对这种术前治疗有反应。目前，对这种治疗的成功监测是基于组织学、内窥镜和放射学评估，但这种监测是不够的。表观遗传学变化在癌症发展和治疗中具有重要作用。在这种情况下，microRNA已被证明是有用的生物标志物，用于分类癌症和提供有关各种癌症类型的化疗和放射敏感性的信息。因此，本提案的目标是研究microRNA在预测食管癌化疗/放射敏感性和监测这些患者新辅助治疗成功中的作用。因此，我们使用细胞培养模型和人类治疗前和治疗后的样本来确定新辅助治疗前后的microRNA表达谱。此外，我们的目标是确定改变的microRNA的可能靶基因。这将使我们能够更好地了解影响对新辅助治疗敏感性的细胞过程。通过这些结果，我们希望为新的诊断和治疗方法提供一个视角，可以影响食管癌的新辅助治疗。

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.