discoveries magazine

The Smoking Gun

A study shows how cigarettes may cause pancreatic cancer — and uncovers a potential way to treat it.

No smoking sign made of smoke.

Photo: Clint Blowers

People outside the medical profession might be startled to learn that tobacco has long been implicated in pancreatic cancer, though until now it was unclear why. According to a recent study, the devil is in the molecular details.

A multicenter research team led by Cedars-Sinai discovered that cigarette smoke triggers a sinister protein chain reaction. "A protein called histone deacetylase activates cancer cells to secrete another protein, IL-6," says Mouad Edderkaoui, PhD, assistant professor of Medicine and Biomedical Sciences at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute. IL-6 interacts with immune cells that normally fight cancer, causing them to promote the growth of pancreatic cancer and increase the risk of its spread.

"Our findings also indicate that smoking helps plant the seeds of aggressive pancreatic cancer in the early stages of the disease. The precancer lesions start interacting and recruiting the immune cells before the tumors are formed," Edderkaoui says.

The work yielded a piece of unexpected good news: A drug approved to treat a form of lymphoma seems to inhibit the protein activation pathway launched by cigarette smoke. This allowed immune cells in rodent models to maintain their original anti-cancer function and stop the development of pancreatic cancer.