Hormones such as estrogen and testosterone are notorious in some cancers for promoting tumor growth. But researchers at Thomas Jefferson University are finding that colorectal cancer may prove to be the rare case where it’s the absence of a hormone that drives the disease.
That hormone, guanylin, binds to a receptor that controls many of the processes that can go awry in an intestinal cell and make a tumor, such as cell proliferation.
In new work published this month in the journal Cancer Epidemiology, Biomarkers & Prevention, Jefferson pharmacologist Scott Waldman and his team measured the amount of guanylin in tissue samples from more than 150 colorectal cancer patients.
“One-hundred percent of the tumors that we looked at lost the hormone guanylin, compared to the normal intestinal cells from the same patients,” said Waldman.
Together with previous animal studies, the results suggest that it’s the loss of guanylin that triggers cells to become cancerous, said Waldman. Consistent with that idea is the increase in colorectal cancer as people age, since natural levels of guanylin begin to drop off around the fifth decade.
The findings also indicate replacement hormone could stop the cancer before it starts.
“It has the potential to take what is now an irreversible genetic disease,” said Waldman, “and it converts that into a reversible endocrine disease.”
The replacement hormone, linaclotide, already exists, and is approved to treat a type of inflammatory bowel syndrome.
The Jefferson team is now testing it in healthy volunteers to see if it produces the expected biological effects. If successful, Waldman said, they will perform a clinical trial to determine if hormone replacement can prevent those with a high risk from developing the disease.
According to the CDC, each year more than 130,000 Americans are diagnosed with colorectal cancer and 50,000 patients die.