The American Cancer Society has awarded a four-year, $729,000 grant to City of Hope’s Joseph Kim, M.D., assistant professor of surgery, to further his pursuit of proteins that appear to promote pancreatic cancer.

Joseph Kim (Photo by Walter Urie)

The funds will enable Kim and his colleagues to study the importance of a chemokine called CXCL12 in pancreatic cancer, one of the most difficult malignancies to treat. The grant advances work currently supported by the National Cancer Institute (NCI) through Kim’s K22 grant.

“A growing body of evidence implicates CXCL12 in the development and progression of pancreatic cancer, and our work will tell us a lot about how it pushes cancer’s proliferation,” said Kim, part of City of Hope’s Gastrointestinal Cancer Program. “We believe the findings potentially will provide the groundwork for testing new therapies or even prevention strategies that target this protein.”

Kim and colleagues already have made several key discoveries relating to CXCL12 signaling in pancreatic cancer. Through their NCI-supported work, they found that CXCL12 activates an important receptor called CXCR4. Although it is normally quiet, this receptor starts going into overdrive in abnormal pancreatic cells when the cells first start forming a lesion. These lesions may eventually develop into pancreatic cancer.

They also discovered that CXCL12 interacts with a second receptor: CXCR7. The new funding will help the team better understand CXCL12’s signaling with both CXCR4 and CXCR7 — and their relationship to another player in the cancer conversation: the oncogene known as K-Ras.

Mutations in K-Ras are common in gastrointestinal cancers; scientists have shown these mutations appear in as many as 80 percent of pancreatic malignancies. Kim and his colleagues are trying to uncover how CXCL12 interacts with K-Ras to promote cancer, and they believe CXCR4 and CXCR7 are involved in different ways.

The team plans to look at this complex web of signaling in a special mouse model that has an early, precursor stage of pancreatic cancer.

“This work is unique because we’re looking at early beginnings of pancreatic cancer,” Kim said. “This is a time when the disease can potentially be cured. Considering the challenge we face in treating pancreatic cancer today, strategies that target these early factors could have great impact.”

About 43,140 people will be diagnosed with pancreatic cancer in the U.S. and about 36,800 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.