Viagra, also known as sildenafil, is best known as a treatment for erectile dysfunction. But a new research study suggests it may also have another surprising use. Researchers found that sildenafil slowed the growth and spread of several types of cancer in laboratory studies and animal models. They also found encouraging signals in patient health records that suggest the drug may be linked to better survival in some people with cancer.
While these findings are exciting, it is important to remember that this research does not show that people should take sildenafil to treat cancer. The study shows promising early evidence that will need to be tested in future clinical trials.
How did sildenafil affect cancer cells?
The researchers tested sildenafil in several mouse and human cancer cell lines, including breast, colon, lung, and prostate cancers. They found that the drug reduced cancer cell survival, slowed cell movement, decreased the ability of cancer cells to form colonies, and reduced the number of metastatic tumors that formed in the lungs of mice.
The researchers also showed that these effects were specific to blocking the PDE5A enzyme. Similar results were seen when another PDE5 inhibitor, vardenafil, was used and when the PDE5A gene was turned off in cancer cells. Human cancer cells responded in a similar way to the mouse cancer cells, suggesting the findings may apply across several tumor types.
A different way of fighting cancer
Rather than attacking cancer DNA directly, sildenafil appeared to interfere with how cancer cells handle cholesterol.
Cancer cells need cholesterol to build healthy cell membranes, produce energy, and spread to other parts of the body. The researchers discovered that sildenafil caused cholesterol to become trapped inside lysosomes, which are small recycling compartments inside cells. As a result, less usable cholesterol reached the parts of the cell that needed it.
Without enough available cholesterol, cancer cells had trouble forming structures called lipid rafts that help cells move and invade surrounding tissue. The cells also showed reduced energy production from their mitochondria, making them less able to spread throughout the body.
Could combining sildenafil with statins help?
The researchers also tested sildenafil together with the cholesterol-lowering drug lovastatin.
Because the two drugs reduce cholesterol availability in different ways, the combination produced stronger effects than either drug alone. In laboratory studies and animal models, the combination further reduced cancer cell growth, migration, and tumor growth while increasing cancer cell death.
The researchers then examined medical records from more than 40,000 male cancer patients. They found that patients taking both statins and sildenafil had better five-year survival than non-users. Higher sildenafil use was associated with greater benefit, although the researchers emphasize that these findings come from observational health records and cannot prove that the medication caused the improved outcomes.
What does this mean for patients?
This study suggests that sildenafil may one day become part of a new strategy to help reduce cancer spread by disrupting how cancer cells use cholesterol. Because sildenafil is already an FDA-approved medication with a well-known safety profile for other conditions, it may be easier to study in future cancer clinical trials.
However, this research does not show that sildenafil is an approved cancer treatment. Most of the evidence comes from laboratory experiments, animal studies, and retrospective analyses of health records. Clinical trials in cancer patients will be needed to determine whether sildenafil is safe and effective for treating cancer.
For now, the findings provide an exciting example of how an existing medication might eventually be repurposed to help fight cancer.
Source
Ariav Y, Hayek S, Cantore T, et al. PDE5a Inhibition Restricts Cancer Metastasis by Disrupting NPC1-Mediated Cholesterol Trafficking Through a Non-canonical cGMP-Dependent Pathway. Cancer Research. Accessed by https://aacrjournals.org/cancerres/article/doi/10.1158/0008-5472.CAN-26-1818/786876/PDE5a-Inhibition-Restricts-Cancer-Metastasis-by
