Molecular Characterization of FGFR2 Fusions in Cholangiocarcinoma
Abstract
Personnel: Liver cancers are considered some of the most deadly tumors, and a better understanding of how normal liver cells become cancerous can lead to new and improved drugs to treat these cancers. My experience in graduate school studying how the liver grows, develops, and responds to injury led me to pursue liver cancer research as a postdoctoral fellow. My career goal is to follow the example of my past and current research mentors to become a principal investigator at a university and conduct liver cancer research full-time while training the next generation of scientists. This award will help support my career by providing funding to address an important medical problem that affects hundreds of thousands of patients. Furthermore, the funds will allow for time-consuming and expensive experiments to model liver cancers in animals and help us gain access to human tumor samples for drug testing that could lead to new treatment options. Research Development: My plan for achieving these career goals will leverage the strengths of my postdoctoral research environment and the training from my mentor, Dr. Nabeel Bardeesy. Dr. Bardeesy is an expert on using mouse models to study liver and pancreatic cancers, and his lab offers many cutting-edge tools for studying these diseases. The Massachusetts General Hospital Cancer Center, where the lab resides, is home to dozens of cancer researchers with varied expertise in all aspects of cancer biology and new experimental tools. We will collaborate with Dr. Andrew Zhu to obtain patient tumor samples, Dr. Wilhelm Haas to compare global protein changes in our mouse models, and Dr. Cyril Benes to discover new drugs to treat liver cancers. Furthermore, becoming an effective communicator is essential for a career as a cancer researcher; therefore, my research development plan also includes opportunities to present my research by participating in departmental seminars, national and international conferences, and by authoring and reviewing grants and publications. Research: Chronic liver diseases, including liver cancers, impact hundreds of thousands of patients. We are interested in a deadly type of liver cancer called intrahepatic cholangiocarcinoma (ICC). For unknown reasons, more and more people are being diagnosed with ICC, which affects the bile ducts of the liver. Patients typically die within 1 year of diagnosis and treatment with chemotherapy has limited effectiveness. The risk factors for ICC are similar to those of other chronic liver diseases, including chronic alcohol consumption, obesity, and viral hepatitis, all of which affect the military personnel and Veterans. There is great clinical need to develop new ways to detect and treat ICC, and improving patient outcomes will require a better understanding of the biology of this disease. Mutations involving IDH1, IDH2, and the FGFR2 genes, which are the focus of this proposal, occur frequently in ICC patients. Genetic changes to FGFR2 cause over-activation of a pathway normally responsible for embryonic development and cell division. Our goal is to understand how these mutations cause cancer and use this information to develop new therapies. These therapies will target only the mutations and therefore only the cancer cells responsible for ICC, sparing other healthy liver cells. We will develop and use new experimental tools, such as a mouse with the same FGFR2 mutation found in humans, to study how these mutations contribute to tumor formation by changing the characteristics of liver cells. For example, ICC cancer cells may divide at a different rate, appear more immature, or exhibit an altered gene expression pattern compared to healthy liver cells. We also have the unique ability to obtain tumor samples from patients undergoing treatment for ICC. Patient tumor samples are invaluable resources to test drug effectiveness and to study cancer cell biology. However, many patients eventually develop resist
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610267
Entities
People
- Leah Liu
Organizations
- Massachusetts General Hospital
- United States Army