Another Use for Viagra: Fighting Colorectal Cancer

According to the American Cancer Society (ACS) colorectal cancer is the third leading cause of cancer death among men and women in the United States. It is the third most commonly diagnosed form of cancer overall; around 1 in 22 men and 1 in 24 women are likely to develop it at some point.

But the release of recent studies have found that the erectile dysfunction drug Viagra (Sildenafil), when administered daily in a small dosage, may significantly reduce the risk of colorectal cancer.

This latest research – published in the journal Cancer Prevention Research – uses a mouse model of this genetic mutation to test the effect of sildenafil — which is marketed as the popular erectile dysfunction drug Viagra — on colorectal cancer risk.

According to the research, a significant risk factor for developing the colorectal cancer is a mutation in a gene called the adenomatous polyposis coli (APC), a tumor suppressor. People with an APC genetic mutation might develop hundreds of colorectal polyps, which may eventually result in cancer.

The study — led by Dr. Darren D. Browning, a cancer researcher at the Georgia Cancer Center and the Department of Biochemistry and Molecular Biology at Augusta University in Georgia — claims that a small daily intake of the drug could cut the number of colorectal tumors by half.

Researchers studying the effects of Viagra (aka sildenafil) on mice have discovered a small, daily dose of the medication in the animals' drinking water significantly reduces their risk of developing colorectal cancer.

"Giving a baby dose of Viagra can reduce the amount of tumors in these animals by half," says biochemist Darren D. Browning from Augusta University.

The sobering numbers on colorectal cancer

Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is defined as the development of cancer from the colon or rectum (parts of the large intestine). A cancer is the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Signs and symptoms may include blood in the stool, a change in bowel movements, weight loss, and feeling tired all the time.

Most colorectal cancers are due to old age and lifestyle factors, with only a small number of cases due to underlying genetic disorders. Other risk factors include diet, obesity, smoking, and lack of physical activity. Dietary factors that increase the risk include red meat, processed meat, and alcohol.

Another risk factor is inflammatory bowel disease, which includes Crohn's disease and ulcerative colitis. Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than five percent of cases. It typically starts as a benign tumor, often in the form of a polyp, which over time becomes cancerous.

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In Europe the five-year survival rate for colorectal cancer is less than 60 percent. In the developed world about a third of people who get the disease die from it.

Survival is directly related to detection and the type of cancer involved, but overall is poor for symptomatic cancers, as they are typically quite advanced. Survival rates for early stage detection are about five times that of late stage cancers.

Colorectal cancer is the second highest cause of cancer occurrence and death for men and women in the United States combined. An estimated 149,000 cases were diagnosed in 2019.

Based on recent research, about five percent of men and women born today in the U.S. will be diagnosed with colorectal cancer during their lifetime. The median age at diagnosis for cancer of the colon and rectum in the U.S. is 69 years of age.

Making the hard choices

In the study, the researchers demonstrated that the daily Viagra dose halved the formation of polyps in mouse tissue: abnormal clumps of cells that form on intestinal lining, which have a tendency to become tumors.

Another drug the researchers experimented with, linaclotide – used to treat constipation and irritable bowel syndrome – was even more effective than Viagra.

But it comes with a downside: diarrhea, even in small doses, which makes it ultimately unsuitable for prolonged use, the researchers say.

In contrast, Viagra at such low doses isn't known to produce side effects in humans, which could make it a safe, convenient way to stop the spread of polyps, thanks to it promoting production of a chemical called cyclic GMP inside the body.

The exact process by which cyclic GMP benefits the intestinal lining is still being investigated, but the research so far suggests the chemical suppresses excessive cell proliferation – the formation of new cells – in the gut.

Viagra is a member of a class of drugs called PDE5 inhibitors. These drugs increase levels of cyclic guanosine monophosphate (cGMP, for short), a substance that contributes to proper functioning of smooth muscle cells throughout the body and helps regulate the homeostasis of the layer of cells in the intestinal lining.

Mutations that cause cancer in those cells can occur randomly through errors in cell division or with exposure to carcinogens in food or other substances that are ingested. By using Viagra (sildenafil) to reduce the number of proliferating cells, “we are proportionally reducing susceptibility to the initiation of cancer,” Dr. Browning says.

While the study found that the suppression of cell proliferation begins within 24 hours after the first dose of Viagra, “the lining of the gut is replaced around every five days, so we believe the maximum protective effect will occur after taking the drug for five days,” Browning notes. But when use of the drug is stopped, the turnover of cells in the intestinal lining reverts back to its original rate.

It may turn out that drugs that can reduce the incidence of polyp formation will prove to be most beneficial for people who inherit genetic mutations that can cause them to develop hundreds to thousands of colon polyps and have a high risk of colorectal cancer as a result, the study concludes.

It’s also possible that other PDE5 inhibitors that have polyp-reducing effects “that are equally safe over the long term might be better for chemo-prevention of colon cancer in people,” Browning adds. Hopefully, time and future clinical trials will provide greater clarity.

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