Israeli Study Finds Viagra May Inhibit Cancer Metastasis by Reducing Cholesterol Availability

A recent study published in the journal Cancer Research by researchers at the Weizmann Institute of Science reveals that sildenafil, the active ingredient in Viagra, may limit cancer cells' ability to spread and form metastases. Led by Dr. Yarden Ariav and Prof. Ayelet Erez, the team discovered a previously unknown mechanism whereby sildenafil reduces cholesterol availability in cancer cell membranes, a critical component for cancer cells to detach, migrate, and invade new tissues.

Originally developed for angina and hypertension, sildenafil’s vascular effects led to its widespread use for erectile dysfunction. Prof. Erez, a pediatric geneticist and dean at the Weizmann Institute’s medical school, noted that the drug’s long-standing safety profile could facilitate its repurposing for cancer treatment. The discovery began with computational analysis identifying the PDE5A gene, which encodes the enzyme PDE5 inhibited by sildenafil, as linked to improved cancer patient survival.

Laboratory tests showed sildenafil significantly impaired cancer cell migration across breast, lung, and colon cancer lines. This effect was replicated with other PDE5 inhibitors but not with inhibitors of related enzymes, confirming specificity. Further investigation revealed cholesterol accumulation in lysosomes within treated cancer cells, disrupting the NPC1 protein responsible for cholesterol transport and reducing membrane cholesterol. This reduction impairs cancer cell flexibility and motility, essential for metastasis.

Animal studies in mice and analysis of human breast cancer tissue samples supported these findings. Collaborating with Clalit Health Services and Rabin Medical Center, researchers analyzed 20 years of medical records from five million insured individuals. They found a statistically significant association between sildenafil use and improved survival among male cancer patients, with greater exposure correlating to better outcomes. This effect was not observed in patients using common antidepressants, suggesting the benefit is not due to mood improvement.

The team also explored combined treatment with statins, cholesterol-lowering drugs, finding the highest survival rates among patients using both medications. However, these observational findings do not prove causation, and controlled clinical trials are needed to confirm efficacy and safety in oncology.

Future research aims to identify which cancer types and disease stages might benefit most, with particular interest in triple-negative breast cancer, a subtype resistant to hormonal and targeted therapies. Prof. Erez emphasized the importance of considering the whole patient, including genetics, microbiome, lifestyle, and concurrent medications, to better understand and treat cancer.