Although non-steroidal anti-inflammatory drugs (NSAIDs) can decrease colorectal cancer incidence, their gastrointestinal toxicity restricts their long-term use in people that are predisposed to colorectal tumor growth, such as those with familial adenomatous polyposis (FAP).
However, researchers at Wyeth-Ayerst Research laboratories have discovered that combining the NSAID sulindac with a new drug that inhibits epidermal growth factor receptor kinase, EKI-569, can substantially reduce the amounts of NSAID required - while being even more powerful at reducing colorectal polyp formation.
Sulindac plus epidermal growth factor inhibitor decrease experimental polyp formation.
Dr Philip Frost and his team, fed mice modeling FAP a combination of the two drugs. They found that this reduced polyp formation by as much as 95% over control animals, far more than either drug alone.
These results suggest that the drug combination could be a powerful new strategy for the chemoprevention of colonic neoplasms, and it may be useful in humans.
In an accompanying News & Views article in Nature Medicine, Raymond Dubois and Rajnish Gupta of Vanderbilt University Medical Center, write, "the results may be a harbinger for the eventual development of effective combinatorial regimens for cancer prevention in humans."
Moreover, they suggest testing the potency of EKI-56 with one of the new COX-2 inhibitor anti-inflammatory drugs. They propose that this combination might be even more powerful.