97 Researchers from the Weizmann Institute of Science, working with Clalit Health Services, have identified a previously unknown biological mechanism suggesting that sildenafil, the active ingredient in Viagra, could interfere with cancer cells’ ability to form metastases. The study, published in the journal Cancer Research, found that sildenafil may block cancer cells’ access to cholesterol, a critical building block that enables tumours to spread throughout the body. It was led by researchers from the Weizmann in collaboration with scientists from Clalit, the US National Cancer Institute, and physicians and researchers from Clalit’s Beilinson and Hasharon Hospitals. The laboratory research, led by Dr Yarden Ariav in the laboratory of Professor Ayelet Erez at the Weizmann, uncovered a previously unknown pathway showing how sildenafil affects cholesterol regulation inside cells. Cancer cells depend heavily on cholesterol to detach from primary tumours and invade other organs. By limiting access to cholesterol, sildenafil may make it harder for tumours to spread. The mechanism involves elevated cGMP and disruption of lysosomal cholesterol trafficking through NPC1, opening avenues for further investigation into PDE5 inhibitors more broadly. The findings also suggest that combining sildenafil with cholesterol-lowering statins may further reduce cancer cells’ ability to obtain or produce cholesterol, potentially strengthening the anti-metastatic effect. Cancer metastasis remains a major challenge in treatment, responsible for most cancer-related deaths. Professor Erez, the study’s senior author, said: “Our study identifies a previously unknown biological pathway that could be exploited to impair the ability of cancer cells to form metastases. It also highlights that cancer biology is influenced not only by mutations within tumours but by the patient’s overall metabolic state, and medications taken for other conditions.” Beyond the laboratory experiments, the research also drew on one of the world’s largest integrated healthcare databases. Researchers from Clalit analysed more than 20 years of anonymised medical records from approximately 5 million members, including a large observational study of 40,000 men diagnosed with cancer. They found that men who had used sildenafil before being diagnosed with cancer had better overall survival than those who had not, with survival even better among patients who had used both sildenafil and statins before their diagnosis. While the findings do not prove that Viagra improves cancer outcomes, they closely matched the biological mechanism discovered in the laboratory. Dr Samah Hayek, co author of the study, said the combination of laboratory science and real-world medical data makes the findings particularly compelling: “This study bridges two worlds. The laboratory identified a promising biological mechanism, while Clalit’s real-world data showed that the same signal may also be reflected in patient outcomes.” Dr Hayek emphasised, however, that the findings should not change medical treatment today: “Our study did not examine whether giving Viagra to patients after they are diagnosed with cancer improves outcomes. It looked only at medication use before diagnosis and its association with survival. These findings are encouraging, but they do not mean cancer patients should start taking Viagra.” She added that answering whether sildenafil could one day become part of cancer treatment will require prospective randomised clinical trials. More than 90 million men worldwide have used Viagra since its approval in 1998, while an estimated 200 million people currently take statins, making both drugs among the most widely prescribed medications globally. The study underscores the value of repurposing existing drugs, given their established safety profiles, for potential new applications in oncology. Researchers caution that the associations identified do not establish causation, and that clinical trials are essential before any changes to patient care. The collaboration between basic-science research at Weizmann and Clalit’s population-health data exemplifies how integrated approaches can accelerate discoveries in cancer research.