The Function of RHOA Mutations in the Development of Diffuse Gastric Cancer
Abstract
Gastric cancer (stomach cancer) kills over 700,000 people every year. One of the two major forms of the disease is called diffuse gastric cancer. This class of the disease has especially poor survival, is prone to rapid metastasis, and is lacking in targets for therapy. Therefore, there is great urgency in the development of new approaches to treat these cancers. As a foundation to establishing new therapies, we must learn about the basic mechanisms that are underlying these cancers and that are critical for the cancer s growth and malignant behavior. Moreover, through this research, I will build towards my own goal of becoming an independent academic investigator working to study and develop new therapies for stomach cancer. I believe my prior Ph.D. training prepares me well for this award and helps position me to an ultimate role as an independent stomach cancer researcher. During my graduate training, I have published four papers in prominent, well-regarded journals describing my studies in the colorectal cancer field. Furthermore, during graduate school, I built key skills in basic molecular and cellular biology and cancer biology that will serve me for my postdoctoral training and beyond. To further add to my training and to develop a new research focus on stomach cancer, I chose to come to the Dana-Farber Cancer Institute at Harvard Medical School to do my training with a leading stomach cancer researcher, Dr. Adam Bass. As my mentor Dr. Bass is also an associate member of Broad Institute, a world-renowned cancer genome institute, we have added resources to complement my training and our research. Through this funding, I will gain added support for my salary support and, furthermore, have added resources and time to focus on my research. This award will also facilitate my ability to perform critical but resource-intensive experiments that will allow to more rapidly develop and refine our hypothesis and bring us to key results regarding diffuse gastric cancer much more efficiently and rapidly. The foundation of our research project and this application is a recent finding from my mentor regarding diffuse gastric cancer. Through the performance of the largest ever study of the genome or DNA mutations present in stomach cancer, he identified a very exciting new class of genomic mutations in a pathway called the RHO pathway in the diffuse subtype of this disease. Notably, the RHO pathway has important roles in how cells are able to migrate, a feature that may be especially prominent in diffuse stomach cancers, as these are highly invasive and metastatic. While these findings regarding RHOA are extremely exciting, we still lack a true mechanistic sense of what these mutations are specifically doing in stomach cancer. If we can understand the action of these new genetic mutations, we can develop new approaches to treat these cancers. Therefore, we will work to develop highly important new mouse models of cancer where we put these RHO mutants in the stomach cells of mice and characterize how these mutants act. Additionally, we will use detailed tools to figure out how these RHO mutants specifically change the activity of cells and promote cancers. Ultimately, the potential clinical application of this work is that allowing development of new targeted therapies for this lethal and poorly treated cancer. Moreover, stomach cancer is of rising incidence in younger patients and is related to a number of infectious and chemical exposures that military members may receive. Therefore, beyond the broad benefits of this work, there may be greater relevance to those in the military.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610454
Entities
People
- Haisheng Zhang
Organizations
- Dana–Farber Cancer Institute
- United States Army