The Role of SOX2 in Barrett s Esophagus Development and Progression to Esophageal Adenocarcinoma
Abstract
Esophageal cancer is a leading cause of cancer death world-wide. It is comprised of two subtypes: squamous cell carcinoma and adenocarcinoma. Alarmingly and for unclear reasons, the rates of esophageal adenocarcinoma have been increasing in the US over the past several decades. Obese Caucasian males over the age of 50 who smoke are more often affected by this disease. Surgery, radiation, and one-size-fits-all toxic chemotherapy remain the mainstay of our current poor treatment of this disease, as only one out of five patients with esophageal adenocarcinoma will live longer than 5 years. Quite simply, we do not know why this disease occurs, how to prevent it from forming, or how to best treat it. What we do know is that there is a precursor condition called Barrett’s esophagus that occurs during the development of esophageal adenocarcinoma. Interestingly, this precancerous condition is defined by replacement of the normal esophagus lining with an intestinal-like lining in response to long term gastroesophageal reflux disease or “heartburn.” If we understand how and why Barrett’s esophagus develops, then we can possibly reverse this condition to prevent it from ever progressing to esophageal adenocarcinoma. I am an oncologist who primarily treats esophageal cancer patients in the clinic, and studies esophageal cancer in the research lab. I am committed to not only understanding the basic science of esophageal cancer, but also, and more importantly, taking new discoveries and translating them into real improvements in the way we treat esophageal cancer patients. My goal is to develop improved detection, prevention, and treatment modalities for esophageal cancer. This award will provide support for my research during this critical time as I develop into an independent scientist and clinician. Specifically, my research proposes to look at a key factor or gene, SOX2, that is needed to maintain a normal esophagus, and is lost upon development of Barrett’s esophagus and during progression to esophageal adenocarcinoma. I believe that SOX2 is needed by the normal esophagus to prevent development of abnormal intestinal characteristics, and its loss is a critical step during the development of esophageal adenocarcinoma. Thus, a novel way to prevent and treat esophageal adenocarcinoma would be to prevent this loss of SOX2. Within the timeframe of this proposal, I plan to study this novel theory and find new drugs/compounds that can prevent SOX2 loss to reverse Barret’s esophagus and stop esophageal adenocarcinoma formation. These new drugs/compounds can be immediately developed into clinical trials through my clinical oncology training and the resources available to me at The Alvin J. Siteman Cancer Center and Washington University School of Medicine. In summary, I seek to study how a key esophageal factor, SOX2 is lost in esophageal adenocarcinoma development, and how prevention of this loss can be leveraged therapeutically. Given the similar demographics affected by esophageal cancer as active duty Service members, Veterans, and other military beneficiaries; my work will greatly support mission readiness by improving esophageal cancer early detection, prevention, treatment, and survivorship.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110523
Entities
People
- Ramon U. Jin
Organizations
- Baylor College of Medicine
- United States Army