Irritable Bowel Syndrome Drug May Be Used To Prevent Colon Cancer In Obese People
Recent studies have found the pill linaclotide, a drug approved by the U.S. Food and Drug Administration in 2012, can effectively treat irritable bowel syndrome, well as chronic idiopathic constipation. And now, a new study published in Cancer Research suggests the drug may also help protect against the development of colorectal cancer in obese patients.
Compared to non-obese people, the risk of developing colorectal cancer is 50 percent greater. Although obesity has long been associated with an increased risk of colorectal cancer — the second leading cancer killer in the U.S. — scientists never quite understood why. They speculated it had something to do with the amount of fat tissue and its associated, unknown metabolic processes, including the fact excess calories can fuel cell energy and growth. However, the present study's results suggest that’s not the case.
Findings from a mice study led by investigators at Thomas Jefferson University revealed a high caloric diet turned off the expression of guanylin, a key hormone produced in the cells lining the intestine, which led to deactivation of a tumor suppressor pathway. They also found replacing this hormone turned the tumor suppressor back on and prevented cancer development, even when mice continued to eat excess calories.
Researchers believe linaclotide (brand name Linzess) could be used as a therapeutic approach to preventing colorectal cancer in obese patients.
"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," Dr. Scott Waldman, senior author of the study, said in a statement.
While Waldman added the loss of guanylin is common among humans and animals with colorectal cancer, morbidly obese patients exhibit an 80 percent decrease in guanylin gene expression compared to non-obese people.
"These findings came as a surprise — we and many other researchers worldwide have been trying to disentangle obesity from development of colorectal cancer," Waldman added. "Calories sit in the middle of these two conditions, but the question of what they were doing has been one of the most perplexing and provocative questions in cancer research. Now we finally have a big clue as to the origin of colorectal cancer in obese individuals and perhaps in other people as well.”
Waldman is already involved in a clinical study testing the dose, side effects and efficacy of Linzess as a hormone replacement therapy.
Source: Lin J, Colon-Gonzalez F, Blomain E, et al. Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin–GUCY2C Paracrine Signaling Axis. Cancer Research. 2016.