Link Between Obesity and Increased Risk for Colorectal Cancer May Be Therapy Target

Link Between Obesity and Increased Risk for Colorectal Cancer May Be Therapy Target
Link Between Obesity and Increased Risk for Colorectal Cancer May Be Therapy Target

A currently approved drug may prevent the development of colorectal cancer, according to researchers who revealed a biological connection between obesity and increased risk for colorectal cancer. The study was published in Cancer Research (doi:10.1158/0008-5472.CAN-15-1467-T).

The risk of developing colorectal cancer is 50% greater in obese people compared with lean people.

"These findings came as a surprise. We and many other researchers worldwide have been trying to disentangle obesity from development of colorectal cancer," said Scott Waldman, MD, PhD, chair of Pharmacology & Experimental Therapeutics at Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia, Pennsylvania, and senior author of the study.

"Calories sit in the middle of these 2 conditions, but the question of what they were doing has been one of the most perplexing and provocative questions in cancer research.”

A key hormone in the intestine, the cell surface receptor guanylyl cyclase C, has its expression turned off by a high caloric diet. This research, in mice, found that genetically replacing guanylyl cyclase C turned it back on and prevented cancer development, even as the mice continued to eat excess calories.

The drug linaclotide (Linzess) is structurally related to the lost hormone. So, linaclotide may be a therapeutic approach to prevent colorectal cancer in obese patients, Waldman explained.

Linaclotide was approved by the FDA in 2012 to treat irritable bowel syndrome with constipation and chronic idiopathic constipation.

"Our study suggests that colorectal cancer can be prevented in obese individuals with use of hormone replacement therapy; much as other diseases associated with hormone deficiency, such as loss of insulin in diabetes, can be treated," reported Waldman, who is also an investigator in a  multisite clinical study testing dose and side effects of linaclotide use in healthy volunteers.

"The beauty of our findings is that while we know the hormone is lost in the obese mice, its receptors are just sitting there waiting to be switched on. And this study demonstrates that if you can prevent hormone loss, you can also prevent tumor development. These findings suggest that a drug like linaclotide, which acts like guanylin, can activate GUCY2C tumor-suppressing receptors to prevent cancer in obese patients," Waldman said.

The study was supported by grants from the National Institutes of Health, the Harvard Digestive Diseases Center, the Pennsylvania Department of Health, and Targeted Diagnostic and Therapeutics, Inc.

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