Chronic inflammation and the chemical silencing of tumor-suppressing genes have long been known to influence development and progression of colorectal cancer.
University of Texas MD Anderson Cancer Center scientists have now established a direct molecular connection between these two important influences. They also tested two drugs, separately and together, with promising results in mice that are genetically engineered to develop colorectal cancer.
Findings by the research team led by MD Anderson Provost and Executive Vice President Raymond DuBois, M.D., Ph.D., are found in advance online publication at Nature Medicine.
Prostaglandin E2 (PGE2), DuBois and colleagues found, promotes the silencing of a variety of tumor-suppressor and DNA repair genes by a process called DNA methylation.
The two drugs used in the animal experiments - the anti-inflammatory agent celecoxib (known commercially as Celebrex®å) and the demethylating agent azacitidine (Vidaza®å) - are both approved for human use.
"These mouse studies make us optimistic that we can extrapolate our data to help treat humans," DuBois says. "Improved understanding of PGE2's roles in cancer progression and the regulation of DNA methylation may provide the basis for developing combination therapy to treat targeted groups of patients, and to prevent cancer from occurring or recurring in high-risk groups."
Nature Medicine paper (paywall alert)
Pharma Strategy blogpost
MD Anderson news release