Viagra has spent nearly three decades known for one specific thing. New research out of Israel’s Weizmann Institute of Science suggests its active ingredient, sildenafil, may have a second, unrelated talent: disrupting how cancer cells access the cholesterol they need to spread through the body.
The study, led by Dr. Yarden Ariav in the lab of Prof. Ayelet Erez, was published in the journal Cancer Research and involved collaborators from the US National Cancer Institute and Clalit Health Services, Israel’s largest healthcare provider.
Key Takeaways
- Sildenafil appears to trap cholesterol inside cancer cells, potentially limiting their ability to break away from a tumor and spread to other organs.
- In mouse models of breast, lung, and colon cancer, sildenafil reduced metastasis, and pairing it with a statin worked even better than either drug alone.
- An analysis of health records from more than 40,000 male cancer patients in Israel found that men who used both sildenafil and a statin had a 31% lower risk of death within five years compared to those who used neither.
- This remains lab and animal research plus observational health data — not a clinical trial — and the researchers are explicit that it’s not ready for real-world use.
How a Blood Pressure Mechanism Ended Up Fighting Cancer
Sildenafil works by blocking an enzyme called PDE5, which normally breaks down a molecule called cGMP. Blocking that enzyme lets cGMP build up — the same chemistry that relaxes blood vessels and gives Viagra its original effect. But the research team found cGMP does something else entirely inside a cancer cell: it binds to a protein called NPC1, which normally acts like a delivery system, moving cholesterol out of the cell’s internal recycling compartment (called a lysosome) to wherever the cell needs it. When cGMP builds up and jams that delivery system, cholesterol gets stuck inside the compartment instead of reaching the rest of the cell. Cancer cells try to compensate by manufacturing their own cholesterol, but it isn’t enough — the cell’s outer membrane grows flimsier and its energy production falters, making it harder for the cell to migrate or invade new tissue.
What the Animal and Cell Studies Showed
Researchers tested sildenafil in mouse models of breast, lung, and colon cancer, and in every case, the drug reduced the number of tumors that spread to the lungs. In the breast cancer model, sildenafil barely affected the size of the original tumor but sharply cut the number of new metastatic growths. To confirm the effect wasn’t a fluke, the team tested a related drug, vardenafil, and got the same result, then directly disabled the PDE5 gene and saw the same drop in spread — evidence pointing to that specific enzyme as the mechanism. The effect held even in mice with severely weakened immune systems, suggesting sildenafil was acting directly on the cancer cells rather than through the immune system. In lab experiments, adding a statin (lovastatin) to sildenafil reduced cancer cell movement and survival further than either drug alone, while leaving healthy, non-cancerous cells largely unaffected.
What the Patient Data Showed
The human portion of the study drew on two decades of health records from roughly 5 million people covered by Clalit Health Services. Men who had filled at least three sildenafil prescriptions in the six months before a cancer diagnosis, and who also used statins, had a 31% lower risk of death within five years compared to men who used neither drug. To help rule out other explanations, the patient group was matched against similar non-users based on income, weight, health conditions, and cancer type, and researchers separately tested an unrelated drug, papaverine, which showed no similar benefit — supporting the idea that the effect is specific to this drug class rather than some other trait shared by Viagra users.
Why This Isn’t Ready for Clinical Use
The researchers are careful to flag real limitations: cancer stage at diagnosis wasn’t tracked in the database, a meaningful gap, and people who obtained sildenafil outside the formal healthcare system weren’t captured at all. Retrospective health-record analysis, however carefully matched, can’t prove cause and effect the way a randomized clinical trial can. Dr. Erez herself has been direct about the current state of the research, describing the findings as “still far from routine clinical practice” and specifically cautioning against patients seeking out the drug for cancer treatment on their own. The National Cancer Institute, which co-authored the work, echoed that caution, stating plainly that more research is needed before this approach could be shown to safely and effectively prevent metastasis in people. No large randomized trial testing sildenafil specifically for cancer has been completed.
What’s Next
Despite the early stage of the research, the combination of lab, animal, and large-scale patient data gives researchers a reasonable case for pursuing formal clinical trials next. Sildenafil already has decades of safety data behind it from its approved uses, which could make it a faster candidate to formally test as a cancer-supporting therapy than an entirely new drug would be — though until those trials happen, it remains a research finding, not a treatment option.
Source: Ariav, Y., Hayek, S., Cantore, T., et al., including Erez, A. (2026). PDE5a Inhibition Restricts Cancer Metastasis by Disrupting NPC1-Mediated Cholesterol Trafficking Through a Non-canonical cGMP-Dependent Pathway. Cancer Research. DOI: 10.1158/0008-5472.CAN-26-1818.