Sildenafil (Viagra) could stop cancer metastasis by blocking cholesterol: Weizmann and NCI study

A study published in Cancer Research suggests that sildenafil—the active ingredient of Viagra—may limit metastasis by interfering with the way cancer cells access the cholesterol. The research, led by the Weizmann Institute of Sciences (Israel) with participation of the National Cancer Institute (NCI) of the United States, combines molecular biology, models in mice and the analysis of millions of medical records. MARGENEZ summarizes the discovery and its limits: it is not a prescription for self-medication or a cure for cancer.

What the researchers discovered

According to the statement from the Weizmann Institute and the coverage of Medical Xpress, the Prof. Ayelet Erez—directed along these lines by Dr. Yarden Ariav— identified a biological pathway until now little explored: sildenafil blocks the enzyme PDE5 (phosphodiesterase type 5), which raises levels of cGMP (cyclic guanosine monophosphate).

This increase in cGMP not only dilates vessels - the known effect on erectile dysfunction - but, according to the study, it also joins the NPC1 protein, responsible for transporting cholesterol within the cell. By altering this transport, the cells tumors would have less usable cholesterol to form membranes, migrate and establish metastasis in organs distant.

Cholesterol is especially critical when cancer tries to break away from the primary tumor, travel through the body and invade distant tissues—a process that consumes a lot of energy and membrane lipids, they explain. J-Wire and Ynetnews.

Laboratory, mice and records of millions of patients

The work published in Cancer Research —full title: PDE5a Inhibition Restricts Cancer Metastasis by Disrupting NPC1-Mediated Cholesterol Trafficking Through a Non-canonical cGMP-Dependent Pathway—combines several lines of evidence:

• Cellular models of different types of cancer: less proliferation and migration in vitro.
• Murine models: reduction of metastatic burden with sildenafil.
• Human tumor cell cultures from patients.
• Retrospective analysis of about 5 million members of the Clalit system (Israel), with data accumulated over about 20 years, according to Ynetnews.

In that observational analysis, cancer patients who had taken sildenafil showed better survival in average, with an additional benefit when the drug was combined with statins—drugs that reduce blood pressure. synthesis of cholesterol in the body. The team's hypothesis: sildenafil limits cholesterol already present in cells and Statins stop the production of new cholesterol, reinforcing the antimetastatic effect.

Researchers from Clalit's innovation division, from the Rabin Medical Center also collaborated (Beilinson and Hasharon) and the laboratory ofProf. Eytan Ruppinin the NCI.

Why cancer cells would be more vulnerable

The authors point out that the effect seems more marked in tumor cells than in healthy cells: by accumulating cholesterol in lysosomes and the lipid “rafts” of the membrane are altered, the malignant cells would reduce their ability to move. In experiments described in previous summaries of the same line of research (AACR conferences), the genetic inhibition of PDE5 mimicked lysosomal trafficking defects similar to Niemann-Pick disease type C (NPC1 mutations).

TheProf. Erez, a doctor as well as a researcher and dean of the Gutwirth Faculty of Medicine at the Weizmann, stressed in the institutional statement that cancer biology does not depend only on tumor mutations, but also on the the patient's metabolic status and medications already taken for other conditions—a “treat the patient” approach completely, not just cancer.

Context: from hypertension to Viagra and now oncology

Sildenafil was originally developed for hypertension and angina, but since its approval in 1998 it became the best-known treatment for erectile dysfunction. The Weizmann figures at about 90 million men have used Viagra in the world; statins are taken more than 200 million people, according to the same statement.

Reusing already approved drugs – a strategy known as drug repurposing – accelerates research because their profile of safety is documented. Even so, a use other than the approved one requires specific clinical trials in oncology.

What the public should NOT interpret

MARGENEZ insists on these limits:

• The study is preclinical and observational in its registry component; does not prove on its own that taking Viagra cure or prevent cancer in people.
• Clalit data show association, not causation: patients taking sildenafil may differ in age, comorbidities or type of tumor.
• There is no approved indication by the FDA, EMA or other agencies for using sildenafil against metastasis.
• Self-medicating with Viagra along with chemotherapy, hormone therapy or statins without medical supervision can be dangerous (interactions, cardiovascular effects, incorrect doses).

The PDE5–cGMP–NPC1 pathway is a promising target for future research, possibly in combination with statins, But oncologists consulted by the media usually ask for caution until prospective randomized trials are available.

Likely next steps

The Weizmann team plans to delve deeper into how the host's metabolic environment modulates tumor progression and whether to inhibit PDE5 It can be integrated into protocols that already use immunotherapy or other lines—areas where Prof. Erez herself has published on metabolism and amino acids at AACR congresses. Any clinical application would require trial design, oncological dosing and monitoring of adverse effects in the cancer population.

Editorial note: This article is informative dissemination based on scientific and specialized press sources. Does not replace An oncologist's advice does not recommend starting, stopping, or combining over-the-counter medications. If you detect a factual error, contact MARGENEZ for review.