Barrett’s esophagus and esophageal adenocarcinoma: from molecular pathogenesis to novel therapeutic targets

Despite latest improvements in diagnostics and therapeutics, esophageal cancer is still the sixth most frequent cause of death related to cancer worldwide. Patients that suffer from this cancer have very poor prognosis, with 5-year survival rates of 15-20%. This is mostly due to late clinical presentation with advance disease. Strikingly, especially in western countries, the incidence of the histologic subtype esophageal adenocarcinoma (EAC) increased dramatically over the past twenty years. Unfortunately, standard treatments, such as chemoradiotherapy and/or surgery, seem to be not effective. In the first part of this thesis, I’ve approached the study of molecular key events involved in the development of Barrett’s esophagus, one of the major risk factor associated with the development of EAC. Specifically, I’ve tried to understand the signalling pathways activated by the chronic gastro-esophageal reflux exposure, in order to unveil novel therapeutic targets at which preventive therapies can be directed. In the second part of this thesis I’ve focused on the immunobiology of EAC. I’ve tested novel methodologies for boosting the host’s anti-tumor immune response and, I’ve attempted to understand molecular mechanisms that can lead to tumor immune evasion. Only a deep understanding of the described molecular pathways can lead the way to the development of more effective therapeutic approaches, such as, immunotherapy.