May 24, 2007 A colon cancer researcher at the Ireland Cancer Center of University Hospitals Case Medical Center (UHCMC) has laid out the roadmap for how medical science should employ aspirin and new aspirin-like drugs for use in preventing colon cancer in certain high-risk individuals.
In the New England Journal of Medicine, Sanford Markowitz, MD, PhD, writes an editorial accompanying research from Dr. Charles Fuchs' team at Harvard Medical School that lays out the hypothesized mechanism by which the use of aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs), also called COX-2 inhibitors, act to decrease the risk of developing colon cancer.
"The compelling evidence that chronic use of aspirin or certain NSAIDS can substantially lower the risk of colon cancer has important implications, especially because colon cancer is the second leading cause of cancer death," writes Dr. Markowitz, the Francis Wragg Ingalls Professor of Cancer Genetics at UHCMC and Case Western Reserve University School of Medicine.
In the Journal article, the Harvard researchers' findings demonstrated that two-thirds of colon cancers have high levels of expression of the COX-2 enzyme, which is blocked by aspirin. Individuals who regularly used aspirin over a course of several years demonstrated a 36% decrease in the risk of developing one of these high COX-2 expressing colon cancers. These results again demonstrated that drugs that block COX-2 can decrease the risk of colon cancer, and demonstrated that such drugs specifically target those individuals whose tumor development is encouraged by the action of the COX-2 enzyme.
Dr. Markowitz' accompanying editorial maps out those studies which will be required to determine the potential use of aspirin in prevention of colon cancer and to determine which individuals might benefit most from taking aspirin or aspirin-like drugs (NSAIDS) such as ibuprofen and Celebrex. Finally, the editorial outlines potential targets for development of drugs that might provide similar protection as aspirin or COX-2 inhibitor drugs for developing colon cancer but with a lesser risk of adverse side effects.
"Interventional trials have shown a decreased risk of the development of colon cancer in high-risk subjects who were given aspirin or COX-2 selective NSAID inhibitors and observational trials have associated a decreased risk of colon cancer with aspirin use," writes Dr. Markowitz in the editorial. "The researchers' findings provide powerful support for the role of COX-2 as a key mediator in the development of colon cancer and now pose questions about the biologic basis and clinical applications of discovering differences that express high or low levels of COX-2."
Dr. Markowitz has done seminal research in the field of colon cancer genetics and prevention. Among his numerous research articles, he published a study on the findings of a new "Celebrex-like" gene that suppresses the grown of colon cancer in the July 2006 issue of Proceedings of the National Academy of Sciences. Dr. Markowitz likens the gene, called 15-PGDH, to a naturally occurring Cox-2 inhibitor such as Celebrex. These findings may lead to the development of a new drug for colon cancer prevention.
"Sandy and his research team have made great strides in colon cancer prevention," says Stanton Gerson, MD, Director of the Ireland Cancer Center at University Hospitals Case Medical Center as well as the Case Comprehensive Cancer Center. "This editorial and all of his proceeding work may have great impact on individuals at high risk for developing this deadly disease."
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