The National Cancer Institute has awarded a $575,000 grant to City of Hope’s Joseph Kim, M.D., assistant professor of surgery, to pursue a protein that spurs pancreatic cancer.
The three-year transition career development award, or K22, will allow Kim and his collaborators to study the protein CXCR4 in pancreatic cancer, one of the most difficult malignancies to treat. It is the first K22 grant awarded to a City of Hope researcher.
|Joseph Kim studies pancreatic cancer origins. (Photo by Paula Myers)|
As Kim explained, CXCR4 is a receptor found on the surface of cells; it usually remains inactive when cells are healthy. But Kim and his colleagues discovered that abnormal pancreatic cells start expressing high levels of the protein when they first begin forming a lesion. These lesions may eventually develop into pancreatic cancer.
Kim and his colleagues will study CXCR4 in a special mouse model that has this early, precursor stage of pancreatic cancer. Last year, the City of Hope researchers showed that the binding of a protein called CXCL12 to CXCR4 in abnormal pancreatic cells in these mice encouraged the abnormal cells to multiply.
The scientists will study exactly how CXCR4 is involved in signaling pathways that may lead to the growth of abnormal lesions, as well as their progression into cancer. By understanding these pathways, they hope to identify drugs that can keep lesions from turning into invasive, metastatic cancer, or perhaps even prevent lesions from developing.
“We plan to test potential therapeutics that target CXCR4 in the mouse model,” said Kim, part of the Gastrointestinal Cancer Program. “If they prove promising, it will bring us a step further toward bringing this strategy to human clinical trials.”
In addition, the researchers will study whether CXCR4 signaling is tied to K-Ras, an oncogene. Mutations in K-Ras are common in gastrointestinal cancers: Scientists have shown these mutations appear in as many as 80 percent of pancreatic malignancies.
Nearly 42,500 people will be diagnosed with pancreatic cancer in the U.S. and more than 35,200 will die of the disease this year, according to the American Cancer Society. Pancreatic cancer is the fourth leading cause of cancer death in the U.S., which makes finding better treatments critical.
City of Hope collaborators include the Developmental Cancer Therapeutics Program’s David Ann, Ph.D., professor of clinical and molecular pharmacology, and senior statistician Paul Frankel, Ph.D., as well as Peiguo “Gerry” Chu, M.D., Ph.D., director of surgical pathology, and surgical postdoctoral fellow Xiaoming Shen, M.D. Surgical oncologist and pancreatic cancer specialist Andrew M. Lowy, M.D., of the University of California, San Diego, is part of the team, as well. Kim noted that Jennifer Davis, manager of the Department of Surgery, also was instrumental in securing the grant.
Transition career development awards support protected time for newly independent investigators to develop and advance their first cancer research programs. The award aims to foster independent research programs among these developing scientists.