When Dr. Yarden Ariav first noticed the pattern in his data, he saw something that surprised even seasoned cancer researchers: patients who happened to be taking Viagra were somehow better at surviving cancer.
The discovery, published in the journal Cancer Research, emerged from the lab of Professor Ayelet Erez at the Weizmann Institute of Science in Rehovot, Israel. Erez, who splits her time between the laboratory and treating patients as a physician, says the finding upended what scientists thought they knew about how cancer spreads.
The researchers discovered that sildenafil, the active ingredient in Viagra, interferes with cancer's ability to metastasize by cutting off its supply of cholesterol. Cholesterol is a waxy substance that all cells need to build their outer membranes, but cancer cells crave it even more when they are trying to break free from a tumor, travel through the bloodstream, and take root in new organs.
The mechanism works like this: sildenafil blocks an enzyme called PDE5, which allows a signaling molecule called cGMP to build up in cells. This cGMP then binds to a protein responsible for ferrying cholesterol around the cell. When that protein gets occupied, less cholesterol reaches where it needs to go. Cancer cells, it turns out, are especially dependent on a steady cholesterol supply, making them uniquely vulnerable to this disruption.
But the most exciting finding came when the team combined sildenafil with statins, drugs that many people already take to lower their cholesterol. In mouse experiments and in cancer cells taken from human patients, the drug pairing appeared to pack a double punch: not only did it limit cancer cells' access to existing cholesterol, it also prevented them from making new cholesterol on their own.
To verify their results, the researchers analyzed medical records spanning 20 years from approximately 5 million members of Clalit Health Services, one of Israel's largest health providers. The data told the same story the lab experiments had shown. Cancer patients who had taken sildenafil lived significantly longer, especially when they combined it with statins.
Erez emphasizes that the work is still in early stages. The findings come from mouse models and computer analysis of patient records, not yet from clinical trials where humans receive the treatment deliberately. But if future research confirms the pattern, it could mean that doctors already have a tool sitting in the medicine cabinet.
"Our study underscores the importance of treating the whole patient, not just the cancer, when tailoring the most effective therapy," Erez said. The research suggests that a patient's metabolic health and the medications they already take for other conditions might quietly influence how their cancer behaves.
The team included scientists from the U.S. National Cancer Institute, Clalit's Innovation Division, and Rabin Medical Center. Their work adds to a growing understanding that fighting cancer may require more than targeting the tumor alone.