| The incidence of esophageal adenocarcinoma and its requisite precursor lesion, Barrett’s esophagus, continues to rise worldwide and in particular in Western countries. While neoadjuvant chemoradiation or peri-operative chemotherapy combined with surgery remains the standard of care treatment for localized esophageal cancer, only those minority of patients who achieve a pathological complete response have a 50% five-year overall survival. Thus, identifying which patients would benefit from esophagectomy remains a research priority. The role of liquid biopsies including exosomes, cell free DNA, and circulating tumor cells as disease-specific biomarkers are being explored. While the addition of targeted therapies (anti-HER2, anti-VEGFR2) to chemotherapy has improved survival in patients with metastatic esophageal cancer, more molecular targets are needed. As with most types of cancer, primary prevention of esophageal cancer may be more effective. Elucidating the molecular mechanism underlying Barrett’s esophagus as well as identifying its cell of origin may lead to development of both chemopreventative and therapeutic strategies for Barrett’s esophagus and esophageal adenocarcinoma. Recent identification of multiple cell populations at the mouse squamo-columnar junction that can give rise to Barrett’s-like metaplasia has provided insight regarding the Barrett’s esophagus cell of origin but raises additional questions about how molecular reprogramming of each could give rise to an intestinalized columnar cell. Biomarkers are also needed to identify which patients with Barrett’s esophagus are at highest risk of progressing to esophageal adenocarcinoma. |
