Taking sildenafil, the active ingredient in Viagra, may do more than improve blood flow — new research suggests the drug could slow the spread of cancer. Scientists at the Weizmann Institute of Science in Israel, together with researchers at the U.S. National Cancer Institute, found that sildenafil can restrict cancer metastasis by interfering with tumor cells' access to cholesterol.
The findings, published by the American Association for Cancer Research, were led by Dr. Yarden Ariav in the laboratory of Professor Ayelet Erez at Weizmann. The team showed that sildenafil, a PDE5 inhibitor, limits the ability of cancer cells to use cholesterol. Cholesterol is essential for the process by which cells break away from the primary tumor and travel to other parts of the body, according to the researchers.
Sildenafil works by blocking an enzyme called phosphodiesterase type 5, or PDE5, and increasing a signaling molecule called cGMP. That molecule is best known for dilating blood vessels, the reason the drug became a successful treatment for erectile dysfunction. The researchers found that cGMP also binds to a protein that transports cholesterol inside cells, reducing the amount of cholesterol available for essential cellular functions. Cancer cells are particularly sensitive to that reduction, they said.
To test the connection, the scientists analyzed human and mouse cancer cells, ran genetic experiments, and examined how genes, proteins, fats, cholesterol and cellular energy interact. They also reviewed 20 years of health records from 5 million members of Clalit Health Services, Israel's largest nonprofit health care provider and health insurer. The combination of laboratory and human data adds weight to the idea that a common medication could have an anti-metastatic effect.
Based on the findings, the researchers propose that pairing sildenafil-like drugs with statins, which lower cholesterol, may help slow the spread of cancer. Reducing tumor cells' access to both existing and newly produced cholesterol could make it harder for cancer to establish new tumors, they said. The idea is that the two drug families attack different parts of the same cholesterol-dependent process.
Viagra, now manufactured and distributed by Viatris, was initially developed to treat high blood pressure and chest pain caused by reduced blood flow to the heart. During early clinical trials, researchers noticed an unexpected effect on erectile function, and the drug became one of the world's best-known prescription medications for erectile dysfunction. The latest findings build on a long-standing interest in repurposing established drugs for cancer treatment.
Erez said in a statement that the findings highlight «the importance of treating the whole patient, not just the cancer, when tailoring the most effective therapy.» She also described the work as additional evidence that cancer biology is shaped by the patient's metabolic state and by medications already being taken for other conditions.
The study authors acknowledged limitations. Much of the evidence came from mouse models, and cancer treatment does not always translate the same way in humans. The human data were observational, meaning they show an association rather than proof of cause and effect. Further research and clinical trials would be needed before doctors could consider using sildenafil as a cancer therapy.