he diagnosis of pancreatic cancer is one of the grimmest an oncologist can deliver. The disease is usually in a fairly advanced stage when caught and tends to move rapidly and inexorably, due in large part to a lack of effective diagnostics and treatments. “The problem is we do not understand the disease at the molecular level,” said Sarah Thayer, HMS instructor in surgery at Massachusetts General Hospital.

She may be moving closer to an answer. Working with colleagues at MGH and the University of California, San Francisco, Thayer found that a gene normally expressed only during the early embryological development of the pancreas is turned on again in patients with pancreatic cancer. The sonic hedgehog (SHH) protein was abnormally expressed in 70 percent of patients with full-blown pancreatic cancers, the researchers report in the Sept. 10 online Nature. SHH was also expressed in precancerous lesions, suggesting that it may play a role in causing the disease.

This is not the first time that SHH has been implicated in cancer. The protein plays a role in certain skin and lung cancers, and it was this involvement that tipped off Thayer and her colleagues to a possible involvement in pancreatic cancer. To further explore this hypothesis, the researchers analyzed the pancreases of mice bred to carry mutant versions of the SHH gene. Sure enough, the mice displayed lesions resembling human precancers.

More exciting still, there is evidence that SHH may help maintain pancreatic cancers as well as instigate them. The researchers were able to stop and even reduce the size of some lesions by giving the mice a chemical that blocks SHH’s downstream partners. They were also able to do this in human pancreatic cancer cell lines.

The chemical they used is not approved for human use, but several drug companies are working on SHH-blocking molecules.

—Misia Landau