Issue of
February 24, 1999

Common painkiller may curb esophageal cancer development

BY RUTH SCHECHTER

Aspirin, touted as the world's wonder drug when it was introduced 100 years ago, may offer new hope in treating certain kinds of cancer. Scientists are developing ways to use aspirin and similar non-steroidal anti-inflammatory drugs (NSAIDs) to inhibit the production of an enzyme that regulates cell growth and proliferation. Stanford researchers have noted increased levels of the enzyme, called COX-2, in esophageal adenocarcinoma, a type of cancer, and in Barrett's esophagus, its new predisposing condition. Refined new versions of NSAIDs may eventually prevent the development of some cancers by inhibiting the production of COX-2.

George Triadafilopoulos, MD, professor and chief of the Gastroenterology Section at Palo Alto Veteran's Affairs Health Care System, is investigating the role of COX-2 in esophageal adenocarcinoma and in Barrett's esophagus to determine which NSAID-like drugs may inhibit its production.

Overproduction of prostaglandins, which occurs in acid reflux disease (a backflow of stomach acid into the esophagus), can lead to the growth of cancer cells in a small group of people with a genetic predisposition to the disease. Triadafilopoulos' research has shown increased levels of COX-2 in Barrett's esophagus, suggesting that the use of selective COX-2 inhibitors in some cases may prevent the disorder from developing into adenocarcinoma.

"Most efforts thus far have focused on trying to block the acid reflux," said Triadafilopoulos. "There is evidence that COX-2 is overexpressed in premalignant situations, so we are looking at how this expression is regulated and how we can block the enzyme early on."

Several years ago, scientists identified two COX enzymes, both of which produce prostaglandins. COX-1 is present throughout the body and primarily makes hormones that help keep the stomach lining intact and the kidneys functioning properly. COX-2 is produced only under certain conditions, and its prostaglandins lead to inflammation and cell growth. Aspirin and NSAIDs inactivate both forms of COX, which can lead to stomach bleeding, ulcers, or kidney damage. If COX-2 inhibitors prove beneficial role in preventing prostaglandin growth, Triadafilopoulos and his associates believe they may offer an alternative therapy with a low risk of complications.

Esophageal adenocarcinoma, used to be rare, but has increased dramatically over the past 20 years and now accounts for about half of all esophageal cancers. Approximately 10,000 people in the United States die each year from the disease, which affects mostly middle-aged, Caucasian men. People with Barrett's esophagus, a condition that develops in response to chronic reflux, have a 30 to 40 times increased risk of developing esophageal adenocarcinoma.

Triadafilopoulos' research is being funded by the Stanford Cancer Council. SR