Overview
- Researchers at the Weizmann Institute with U.S. NCI collaborators reported that sildenafil, a PDE5 inhibitor, impaired cancer cell migration by disrupting how cells move cholesterol inside lysosomes.
- Lab work found raised cGMP levels from PDE5 inhibition bind the lysosomal transporter NPC1, reduce cholesterol export, and weaken membrane and mitochondrial functions that tumors use to seed metastases.
- Mouse models and human tumor cell cultures showed lower metastatic burden with sildenafil, and combining the drug with statins produced stronger anti‑metastatic effects in experiments.
- A retrospective analysis of about 20 years of records from roughly 5 million Clalit Health Services members found an association between sildenafil use and better survival, especially when paired with statins, but this is observational and not proof of cause.
- Investigators and the NCI emphasize the evidence is preliminary, that mouse results may not translate to people, and that randomized clinical trials are required before sildenafil or drug combinations should be used to prevent or treat metastasis.