Rational Therapies for Diffuse-Type Gastric Cancer
Abstract
Cancer of the stomach, a 2016 PRCRP Congressionally Directed Topic Area, remains to be a significant treatment challenge. In the United States, 24,500 new cases are diagnosed each year and nearly half of the patients eventually die from the disease. Diffuse-type stomach cancer is a particularly aggressive form of the disease that affects frequently you people, spreads quickly to other organs, and does not respond well to currently available treatments. Therefore, new treatments that take the specific biologic properties of this disease type into account are urgently needed. With this proposal we will pursue one very promising avenue of research that could lead to the development of highly active therapies. This is based on the recognition that in many cases, diffuse-type stomach cancer cells carry mutations of the E-cadherin gene, resulting in very mobile cells that can infiltrate surrounding tissues easily. By analyzing publically available data on changes in the DNA of stomach cancers, we identified cellular pathways that might be responsible for the aggressive behavior of this disease. Thse include the transforming growth factor beta pathway and related pathways. We propose to use advanced methods to manipulate DNA in cancer cells which would allow us to better understand the molecular wiring within these cells and to identify possibly effective treatments, including drug combinations, that target the transforming growth factor beta pathway and other pathways identified through this work. We will test these treatments in cell lines and in mouse models of cancer that utilize tissues directly obtained from patients suffering from diffuse-type gastric cancer. The ultimate goal of this research is to set the stage for the development of new treatment concepts that can be directly tested in human patients as part of clinical trials. Such trials could be designed towards the end of the funding period of this project. Since Drs. Korn, and Janjigian are both physician scientists experienced in the design and conduct of clinical trials, we expect that any findings from these studies can be translated into clinical trials expeditiously, likely within 2.5 years from the start of the project. The hope would be that these new treatments not only stop the growth of the cancer but also result in meaningful prolongation of life. Military Relevance and Impact Military personnel are exposed to an increased risk of infection with the bacterium H. Pylori, which can live in people s stomach for a long time. The bacteria produce factors that can cause DNA damage resulting in stomach cancer, including diffuse-type cancer. Such strains are more common abroad, including Asia and Africa. In addition, living in close proximity with infected people can increase the chance of infection. Thus, service members and their families are at increased risk to develop stomach cancer. The studies proposed here will set the stage for the development of better treatments for this devastating disease which will directly positively impact the life of our military personnel and their families.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710450
Entities
People
- Michael Korn
Organizations
- United States Army
- University of California, San Francisco