Treatment and Response Targets for Helicobacter-Associated Gastric Cancer
Abstract
Stomach cancer is a lethal disease. Most new cases are diagnosed when the cancer has already spread to other organs and as a result, many patients die within 2 years. New ideas for the treatment of stomach cancer are desperately needed. Helicobacter is a bug that lives in the stomach causing inflammation, which can then lead to stomach cancer. We recently developed a unique and clinically relevant model of Helicobacter-associated stomach cancer. We found in our model that certain genes are dramatically upregulated in stomach cancer tissue, which points to previously unexplored tumorigenic pathways that may cause or promote stomach cancer growth. We plan to transplant human stomach tumors into mice without functional immune cells (nude mice, “xenografts”) to test if therapeutics that target these genes will stop tumor growth. Based on our previous work, we have identified a number of therapeutics that target the pathways we found to be upregulated, and we will treat tumor-bearing mice with these drugs. If we find that the tumors respond to these therapeutics, we will inject human stomach cancer-derived tumors directly into the wall of nude mice to test successful drugs that can stop the cancer from spreading. We believe that these studies may point to new treatment options for stomach cancer, thereby repurposing drugs that are already approved for the clinic. Further, we plan to check whether some of the genes we found to be upregulated, especially those that are linked to immune response can identify a patient likely to respond well to a drug. We will do this by using gastric cancer patient samples stored at the tissue biobank at the UCSD’s Moores Cancer Center biorepository core and tumors harvested from the xenografts. We will check the levels of these immune response related genes to see if they can forecast response to treatment by comparing the levels of the genes with the size of the tumor. We believe that the research we plan to do will be meaningful to Veterans, other military beneficiaries, the American public, and especially active duty Service members who have a higher chance of being exposed to infection with H. pylori when they travel to places with high incidences of H. pylori infection like Africa and Asia. In addition, because we propose to use available US Food and Drug Administration (FDA)-approved and experimental drugs to test whether our genes are good targets for treatment, outcomes of our study can be quickly expedited to be tried in gastric cancer patients. This approach does not only cut costs involved with developing new drugs, but it also speeds up the process of making these treatments available to gastric cancer patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010675
Entities
People
- Marygorret Obonyo
Organizations
- United States Army
- University of California, San Diego