Improved Combination Therapies for Bowel Cancer Approaching Reality

New finding by researchers show molecular connection between chronic inflammation and DNA methylation, a process that shuts down cancer-fighting genes, which could eventually pave the way for better combination therapies for treating and preventing colorectal cancer.

In animal experiments, scientists at The University of Texas MD Anderson Cancer Center found that prostaglandin E2, a chemical that promotes inflammation, accelerates the development of colorectal cancer by shutting down genes that suppress tumours and repair damaged DNA.

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Colorectal cancer is a cancer that starts in the colon or the rectum. Colorectal cancer is the third most common cancer in men.

They also found that while either an anti-inflammatory drug or a demethylating agent reduced the size and number of tumours in mice with colorectal cancer, the most powerful response occurred when both drugs were used together.

"We've known that chronic inflammation increases the risk of developing cancer and progression of disease," said senior author Raymond DuBois, M.D., Ph.D., provost and executive vice president at MD Anderson.

"We've also known that tumor-suppressing genes are silenced in human colorectal cancer. However, nobody had made a molecular connection between these inflammatory mediators and changes in gene expression or silencing of genes through affects on DNA methylation."

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Colorectal screening is done using tests to detect blood in stool, colonoscopy or sigmoidoscopy ordouble contrast barium enema or CT colonography.

The two drugs used in the animal experiments - the anti-inflammatory agent celecoxib (known commercially as Celebrex) and the demethylating agent azacitidine (Vidaza) - are both approved for human use.

"One potential application of our research would be a clinical trial for patients who are at extremely high risk for developing colorectal cancer, such as those with a genetic predisposition, to see if treatment with these agents would decrease their risk," DuBois said.

Colorectal Cancer Screening with Colonoscopy
Colonoscopy is a widely used endoscopic procedure to screen individuals for colorectal cancer. It is very sensitive in detecting colorectal cancers.

"These mouse studies make us optimistic that we can extrapolate our data to help treat humans.

"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," DuBois added.

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Flexible sigmoidoscopy is an endoscopic procedure used to screen individuals for colorectal cancer suspected to be in sigmoid colon.

The study has been recently published in the advance online publication of the journal Nature Medicine.

Source-ANI