Overcoming chemoradiation-induced resistance in esophageal cancer

Esophageal cancer is a highly aggressive type of cancer and the sixth leading cause of cancer-related deaths globally. It is characterized by a poor prognosis and merely 20% of patients survive five years after diagnosis. One of the reasons for the poor outcome and metastases formation is the development of treatment resistance. The focus of this thesis was to identify resistance mechanisms in esophageal tumors and develop the means to overcome these. By using multiple esophageal disease models, including patient-derived xenografts (PDXs), primary cultures and organoid cultures, we unraveled multiple resistance mechanisms induced by chemoradiation in esophageal cancer. We identified numerous contributing factors (i.e. IL-6, NANOG, HMGA2 and ESRRA) and explored targeting them to overcome therapy induced resistance in esophageal cancer. Importantly, these findings contribute to a deeper understanding of the diverse mechanisms of resistance that preclude effective treatment of esophageal cancer. The knowledge gained from thesis facilitate the development of novel treatment regimens for esophageal cancer patients, ultimately improving their prospects for successful outcome.