Testing Combination Therapy Could Reveal Clues to Biology of Pancreatic Cancer ► NCI Cancer Bulletin for June 26, 2012 - National Cancer Institute

NCI Cancer Bulletin for June 26, 2012 - National Cancer Institute

Testing Combination Therapy Could Reveal Clues to Biology of Pancreatic Cancer

A small number of patients with advanced pancreatic cancer have responded to an experimental treatment regimen in which a targeted drug is given alone and then in combination with chemotherapy. Although they are preliminary, the results suggest that some patients with this deadly disease may benefit from the regimen, researchers reported at the Pancreatic Cancer: Progress and Challenges meeting, held June 18–21 in Lake Tahoe, NV.

The 18 trial participants initially received vismodegib (Erivedge) alone for several weeks and then vismodegib plus gemcitabine. After 3 months, half of the patients showed no disease progression or had a partial response. Vismodegib, a pill that is approved for some patients with skin cancer, inhibits the Hedgehog signaling pathway, a growth-promoting pathway that is inactive in most adult tissues but switched on in some pancreatic cancer cells.

The activated Hedgehog pathway may also help prevent chemotherapy drugs from reaching pancreatic tumors by contributing to the development of dense stromal cells around tumors, explained lead investigator Dr. Edward Kim of the University of Michigan Comprehensive Cancer Center at a press briefing. Vismodegib, he suggested, has the potential to alter these cells in a way that makes chemotherapy more effective.

But Dr. Kim noted that even if the combination therapy benefits the patient for a time, cancer stem cells within pancreatic tumors may lead to resistance. These cells are thought to have the ability to self-renew. Previous studies have indicated that the Hedgehog pathway may be more active in pancreatic cancer stem cells than in other pancreatic tumor cells.

A goal of the current trial is to learn whether targeting the Hedgehog pathway in pancreatic cancer stem cells might benefit patients. A comparison of biopsies taken before and after starting vismodegib could show the effects of the drug on the Hedgehog pathway and reveal which patients are most likely to benefit from the regimen.

A trial of another Hedgehog inhibitor in pancreatic cancer was recently stopped after negative results. So it will be important to learn more about this pathway and its role in pancreatic cancer, noted Dr. Daniel Von Hoff of the Translational Genomics Research Institute, who moderated the press briefing.