A new study published in Cancer Research concluded that they have discovered the biological previously unfound connection of a long known association between obesity and an increased risk of colorectal cancer. They have also identified an approved drug that might prevent the cancer in obese people.
In research they found that a high caloric diet turned off expression of a key hormone in the intestines, which lead to deactivation of a tumor suppressor pathway. Genetic replacement of that hormone turned the tumor suppressor back on and prevented cancer development even when mice continued to eat excess calories. The drug that was used was linaclotide (Linzess) that is structurally related to the hormone and may be a therapeutic approach to prevent colorectal cancer in obese patients. The researchers said “Our study suggests that colorectal cancer can be prevented in obese individuals with the use of hormone replacement therapy.”
In the study they used genetically engineered mice on different diets and found that obesity (either from excess fat or carbohydrate consumption. or both, is associated with loss of the hormone guanylin, that is produced in the intestine’s epithelium or cells lining the intestines. The hormones turn on its receptor guarylyl cyclase (GUCY2C) that regulates processes underlying regeneration of the intestinal epithelium. “The lining of the intestines is very dynamic and continuously being replaced, and the GUCY2C contributes to the choreography of the key processes needed for thus regeneration.” Deactivation of the guanylin gene is common in colorectal cancers in both humans and animals and morbidly ovese patients echibit an 80% decrease in Guanylin gene expression compared to lean people.
In this study they found the consequence of that loss is that , and without the hormone, the receptor is silent. the guanylin hormone receptor acts as a growth-controlling tumor suppressor happening early in the cancer development. “When the receptor is silenced, the epithelium becomes dysfunctional, setting up the conditions for cancer development.” The research demonstrates that obese mice, compared to lean mice, were much more likely to silence the hormone and its receptor, “We believe that if colorectal cancer is going to develop, it will be through this silencing mechanism-and that it will happen much more frequently in the obese.” This study demonstrates that if you can prevent hormone loss, you can also prevent tumor development and a drug like guanylin, can activate GUCY2C tumor-suppressing receptors to prevent cancer in these patients.
Researchers have already started multi site clinical studies testing dose and side effects of linaclotide use in healthy volunteers.