Researchers make discovery in colon cancer prevention.

A new study finds that individuals who have low expression of the "Celebrex gene," 15-PGDH, are actually resistant to Celebrex treatment when used to prevent colon cancer. The study, published in this week's issue of the Proceedings of the National Academy of Sciences (PNAS), is by Sanford Markowitz, M.D., Ph.D., the Markowitz-Ingalls Professor of Cancer Genetics at the Case Western Reserve University School of Medicine and an oncologist at the Ireland Cancer Center of University Hospitals Case Medical Center and his colleagues (see also Case Western Reserve University).

"These findings have two important practical implications," said Markowitz, who is also an investigator in the Howard Hughes Medical Institute. "First, they suggest that measurement of 15-PGDH may identify which individuals are most likely to benefit from treatment with Celecoxib as a colon tumor preventative. Second, they suggest that identifying drugs that could increase 15-PGDH expression in the colon could be a potent new strategy for preventing development of tumors in the colon."

In the Adenoma Prevention with Celecoxib (APC) trial, a clinical trial conducted by Monica Bertagnolli, M.D. at the Harvard Brigham and Women's Hospital and designed to test Celecoxib for the prevention of sporadic colorectal adenomas, the researchers showed that Celecoxib (brand name Celebrex, a Cox-2 inhibitor that relieves pain and inflammation without harming the digestive tract) treatment of individuals who had previously developed colon adenomas cut the rate of developing new adenomas by one-third, and cut the rate of developing new large adenomas by two-thirds. Some individuals however proved resistant to Celecoxib treatment and developed new colon tumors even while on the drug. Colon adenomatous polyps are benign tumors that are the immediate precursors of colon cancers.

Previous studies by Markowitz published in PNAS (December 2004 and July 2006) discovered that the gene 15-PGDH is expressed by the normal colon and acts similarly to Celecoxib in preventing colon tumors by inhibiting the COX-2 ...