A City of Hope researcher is zeroing in on a key protein that helps pancreatic cancer grow and spread, research that could lead to much-needed drugs against this difficult malignancy — thanks in part to support from the Susan E. Riley Family Foundation.
The foundation has awarded Joseph Kim, M.D., a two-year, $165,000 grant to study CXCR4 in pancreatic cancer. Growing evidence indicates that CXCR4 plays a major part in the cancer’s growth from its very beginnings.
More than 37,000 people will be diagnosed with pancreatic cancer in the United States and more than 33,000 will die of the disease this year, according to the American Cancer Society.
While surgery can successfully treat many early cases of pancreatic cancer, most tumors are discovered at a later stage. And though a new chemotherapy recently was added to the arsenal against pancreatic cancer, such therapies have traditionally only shown modest effects — which explains, in part, why pancreatic cancer is the fourth leading cause of cancer death in the U.S.
The disease calls out for better treatments, and Kim is looking for answers. “We know that cancer development and metastasis involves a variety of factors, but we believe CXCR4 is especially important in the initial development of pancreatic cancer,” said Kim, assistant professor in the Division of Surgery.
A few years ago, Kim happened upon CXCR4, a seemingly obscure but intriguing molecule, during an Internet search. A receptor found on the surface of cells, CXCR4 is normally inactive in healthy cells; but he and colleagues soon discovered that it helps colorectal cancer spread. A growing body of research since has shown much more.
Most recently, Kim and his colleagues found that cells begin to express high levels of the CXCR4 protein at pancreatic cancer’s beginnings, when abnormal cells first begin to form a lesion. It also is active throughout pancreatic cancer’s process of development and metastasis.
Kim and his colleagues now are studying CXCR4 in a special mouse model that has this early, precursor stage of pancreatic cancer. In these mice, a protein called CXCL12 binds to CXCR4 and appears to contribute to the development of the very early stages of pancreatic cancer. They are treating the mice with a drug that binds to and blocks the CXCR4 receptor. Once they better understand how CXCR4 and the signaling pathways work, they aim to create a new and better therapeutic agent targeting CXCR4.
The Susan E. Riley Family Foundation was created by the estate of Susan E. Riley, a Los Angeles-area lawyer who died of pancreatic cancer. Kim’s CXCR4 research also has been supported by the Hirshberg Foundation for Pancreatic Cancer Research.