( The unchecked activity of a cell signal...)Liver cancer linked to cellular repair pathway

Because the pathway, called Hedgehog, is present only in immature, stem-like liver cells, the discovery offers hope for targeted treatment of liver cancer, one of the leading causes of cancer-related death in the world. Laboratory experiments show that blocking the Hedgehog pathway kills cancer cells but leaves mature healthy liver cells intact, the researchers report. Treating patients with medications to interrupt the pathway would likely eliminate the cancer cells while sparing healthy liver tissue, said Jason Sicklick, M.D., a postdoctoral fellow at Duke and lead author of the study.

"Currently, there are no good chemotherapies for liver cancer, and many people with advanced liver disease are too ill for surgery to remove tumors," Sicklick said. "There is a desperate need for effective anticancer treatments that are safe for patients with liver disease."

The results will be published in the April 4, 2006, issue of Carcinogenesis. The research was funded by the National Institutes of Health.

Finding the overactivated Hedgehog pathway in liver cancer, but not in mature liver cells, also opens the door for development of new diagnostic tests for the disease, Sicklick said. "Signs of excessive Hedgehog activity in cirrhotic patients could alert us to early stages of liver cancer, as well as provide valuable prognostic information for patients," he said.

Sicklick and colleagues also discovered a new Hedgehog pathway mutation in a patient with liver cancer that may lead to overactivation of Hedgehog and trigger abnormal cell growth, promoting cancer development. In test tube and cell culture experiments, blocking the Hedgehog pathway reduced growth of cancer cells by over 90 percent.'"/>

Source:Duke University Medical Center