UT Southwestern docs receive grants for innovative studies on lung cancer pathways, drug therapy

Two UT Southwestern doctors have received more than a half-million dollars in grants from the Department of Defense for innovative studies on lung cancer pathways and to test the effectiveness of a potentially less expensive drug therapy.

Dr. James Kim, Assistant Professor of Internal Medicine, received a $250,000 grant to study the "hedgehog" pathway, a critical signaling pathway in normal tissues and in many cancers. Dr. David Gerber, Associate Professor of Internal Medicine, received a $410,000 grant to study the effects of the drug itraconazole on the hedgehog and other pathways. Both are faculty members in UT Southwestern's Harold C. Simmons Cancer Center, the only National Cancer Institute-designated cancer center in North Texas and one of 66 nationwide.

"We think tumors hijack the hedgehog signaling pathway that is normally active during development and in the repair of injured tissues and then use the pathway for their own purpose, which is to grow," said Dr. Kim, who received a Career Development Award designed to encourage and assist promising researchers in the early stages of their careers. "We will test the idea that interfering with the hedgehog pathway will disrupt communication between tumor cells and their surrounding environment and thus slow the cancer's growth."

Originally developed as an anti-fungal medication, itraconazole is less expensive than many cancer drugs and already approved by the Food and Drug Administration for non-cancer treatments in thousands of patients, so its effect on people is well known and the drug has an established safety record.

"The repurposing of an existing drug such as itraconazole is an excellent opportunity for oncology drug development," said Dr. Gerber, co-leader of the Experimental Therapeutics Program in the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.  "Because the drug already has an established safety record and dosing regimen, we can focus on the drug's efficacy and biologic effects early on."

All of the hedgehog pathway inhibitors that have been developed for cancer are still on patent and cost several thousand dollars per month, Dr. Kim said. Itraconazole, on the other hand, costs a fraction of these other agents, said Dr. Gerber.
 
Itraconazole is considered promising because the drug also appears to inhibit angiogenesis, which is the growth of new blood vessels required to deliver oxygen and nutrients to cancer cells. Cancer researchers have long focused on targeting angiogenesis as a way of stopping tumor development.

Dr. Gerber's planned study will use blood tests, tumor biopsies, and MRI scans before and after itraconazole therapy to determine the drug's effects on angiogenesis and the hedgehog pathway. In addition, researchers will track itraconazole levels in blood and tumor tissue, and determine if the tests can predict which patients are most likely to benefit from itraconazole therapy.

The Department of Defense has begun funding research to fend off expected increases in lung cancer among veterans. Compared to civilians, veterans have twice the incidence of lung cancer and have lower survival rates from the disease, Dr. Gerber said. According to a 2009 Institute of Medicine estimate, just over 20 percent of the U.S. population smokes, while 22 percent of veterans smoke and 32 percent of active-duty military personnel smoke.           

Source: UT Southwestern