A drug known to millions as a treatment for erectile dysfunction may have a very different potential role in medicine. New research suggests that sildenafil, the active ingredient in Viagra, could interfere with the ability of cancer cells to spread by disrupting the way they access cholesterol.
The discovery comes from an international research team led by scientists at the Weizmann Institute of Science in Israel. Researchers found that sildenafil may restrict the ability of cancer cells to form metastases through a biological mechanism linked to cellular metabolism.
Sildenafil inhibits an enzyme called PDE5, increasing levels of the signaling molecule cGMP. This mechanism is responsible for the drug’s well-known effect on blood vessels, but researchers discovered that increased cGMP also affects the transport of cholesterol inside cells.
As a result, some cholesterol becomes trapped inside cellular structures known as lysosomes, making it less available for use elsewhere in the cell.
This appears to be particularly important for cancer cells. Cholesterol is an essential component of cell membranes and is involved in processes that allow tumor cells to break away from a primary tumor, migrate through the body and invade distant organs.
When their access to cholesterol is disrupted, cancer cells have greater difficulty migrating and forming metastases. The researchers observed this effect in human cancer cell cultures and animal cancer models.
Even more intriguing results emerged when sildenafil was combined with statins, the widely prescribed drugs used to lower cholesterol. The two medicines target the problem from different directions: sildenafil interferes with access to existing cholesterol inside cells, while statins reduce cholesterol production.
The scientists also examined health records collected over roughly 20 years from about five million members of Israel’s Clalit Health Services. Statistical analysis found improved survival among certain cancer patients who had taken sildenafil, with a stronger association among those who also used statins.
This does not, however, prove that Viagra treats cancer.
The health-record analysis identifies an association rather than a confirmed cause-and-effect relationship. The research was also not a clinical trial in which cancer patients were given sildenafil specifically as an anticancer treatment.
The findings therefore do not mean that people with cancer should begin taking Viagra or statins on their own. Controlled clinical trials will be necessary to determine whether the effect works in patients, which cancers might respond and what doses could be safe and effective.
The discovery is also an example of drug repurposing – investigating whether medicines that have already been approved for one condition could be useful against another.
Viagra itself already has an unusual history. Sildenafil was originally investigated for cardiovascular conditions before its effect on erections transformed it into one of the world’s best-known medicines.
Researchers may now have identified another potential use, this time involving one of the most dangerous aspects of cancer: the ability of malignant cells to spread from the original tumor to distant organs.
For now, Viagra is not a cancer treatment. But the newly identified mechanism could provide scientists with another route toward developing future therapies designed to restrict metastasis.
Sources: Cancer Research, Weizmann Institute of Science.
