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According to peer-reviewed research published in July in Cancer Research, sildenafil—the active ingredient in Viagra—disrupts cancer cells’ cholesterol supply to stop the spread of metastases. Researchers at the Weizmann Institute of Science, alongside teams from the US National Cancer Institute and Clalit Health Services, found that the drug targets the protein transporting essential cholesterol fuel, supported by population-scale data from 5 million patients.
Biological Mechanism: How Sildenafil Halts Cholesterol Transport
Dr. Yarden Ariav led the research in Prof. Ayelet Erez’s lab at the Weizmann Institute of Science, alongside investigators in Prof. Eytan Ruppin’s lab at the US National Cancer Institute, the Innovation Division at Clalit Health Services, and physicians at Clalit-Beilinson Hospital. Using high-resolution cellular imaging on male and female mouse models and human cancer cell cultures, the team tracked how sildenafil acts on cellular pathways.
According to the findings, the active ingredient immediately obstructs an enzyme known as phosphodiesterase type 5 (PDE5). This obstruction triggers a spike in a key chemical messenger called cyclic GMP (cGMP). The cGMP then targets and traps a protein responsible for transporting cholesterol. Deprived of this crucial material, cancer cells in laboratory tests involving triple-negative breast cancer, melanoma, and lung cancer lost their ability to invade other organs.
“We uncovered a new biological pathway and showed how this pathway can be harnessed,” said Erez, who also serves as a senior researcher and dean of Weizmann’s Miriam and Aaron Gutwirth Medical School.
Did you know? Sildenafil was initially developed to open blood vessels for heart conditions before gaining approval for erectile dysfunction in 1998. The new Weizmann Institute study reveals it also impacts intracellular cholesterol trafficking in cancer cells.
Combining Sildenafil and Statins to Prevent Cancer Spread
Laboratory tests revealed that cancer cells activate a compensatory system when deprived of mobile cholesterol, producing more cholesterol independently. To counter this, the research team introduced statins—a common class of cholesterol-lowering drugs taken by more than 200 million people worldwide, according to Johns Hopkins University.
The combination of sildenafil and statins worked in tandem during the experiments, maintaining low cholesterol levels and preventing the cancer from spreading further. Dr. Ido Wolf, head of the oncology division at Tel Aviv Medical Center and head of Tel Aviv University’s medical school, who was not involved in the study, noted that metastatic cancer cells critically depend on cholesterol.
“Disrupting its intracellular trafficking represents a previously unrecognized therapeutic vulnerability,” Wolf explained, adding that the research demonstrates the potential for rapid drug repurposing using widely available medications.
Real-World Patient Data Confirms Laboratory Results
To validate the laboratory models, the Weizmann researchers collaborated with Dr. Samah Hayek, senior epidemiologist at Clalit Health Services and senior lecturer in Tel Aviv University’s Department of Epidemiology and Preventive Medicine. Hayek analyzed data collected over 20 years from approximately 5 million Clalit members.
The analysis showed that survival rates were highest among patients who took both sildenafil and statins six months before their cancer diagnosis. “We used different statistical and epidemiological methods to adjust for many different factors, and found that the results were consistent with what the Weizmann researchers saw in their mouse modeling,” Hayek stated.
Erez emphasized that the real-world patient data confirmed findings for lung, colon, and prostate cancer in male mice. The next phase of research requires pushing medicine forward by testing the treatment in women.
“The uniqueness and the most important thing that we now need to do is a clinical trial to give Viagra to women with triple-negative breast cancer,” Erez said.
Frequently Asked Questions
How does Viagra help stop the spread of cancer?
According to researchers at the Weizmann Institute of Science, sildenafil disrupts cancer cells’ cholesterol supply by trapping the protein responsible for transporting it, depriving the cells of the fuel they need to metastasize.
What role do statins play in this research?
When cancer cells attempted to produce their own cholesterol after sildenafil blocked external supplies, researchers introduced statins to maintain low cholesterol levels and successfully prevent the cancer from spreading.
What types of cancer were studied?
The laboratory tests focused on triple-negative breast cancer, melanoma, and lung cancer, while patient data confirmed findings related to lung, colon, and prostate cancer.
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