In world first, Israeli scientists find active ingredient in Viagra may stop cancer spread

Reporter at The Times of Israel

In a surprising discovery, Israeli researchers say they have uncovered the biological mechanism in which Viagra, a drug best known for treating male erectile dysfunction, helps stop the spread of cancer.

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In peer-reviewed research, scientists at Weizmann Institute of Science showed that sildenafil, the active ingredient in Viagra, disrupts cancer cells’ cholesterol supply, a crucial material they need to metastasize to other organs.

Dr. Yarden Ariav led the research in Prof. Ayelet Erez’s lab at Weizmann, along with researchers in Prof. Eytan Ruppin’s lab at the US National Cancer Institute, the Innovation Division at Israel’s national health provider Clalit Health Services, and physicians and scientists from Rabin Medical Center.

The scientists’ findings, which appeared inJuly in Cancer Research, were based on mouse cancer models, cultures of cancer cells from human patients, and data collected over 20 years from some 5 million Clalit members.

Survival rates were highest among the patients who had taken both sildenafil and statins, a common class of cholesterol-lowering drugs, six months before their diagnosis, the data showed.

The laboratory tests focused mostly on cancers such as triple-negative breast cancer, melanoma, and lung cancer.

The real-world patient data “confirmed our findings in male mice for lung, colon and prostate cancer,” Erez told The Times of Israel by telephone.

She emphasized that the next step is to “push medicine” by giving women a drug traditionally associated with men’s health.

“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.

Sildenafil was initially developed to treat heart conditions because it opened blood vessels. Then, doctors realized it could also effectively treat male erectile dysfunction, and was approved for that use in 1998.

Now, the research team gave the drug to both male and female mouse models and human cancer cells. Using high-resolution cellular imaging to observe and track the changes in real time, the scientists saw how the drug acted quickly, immediately obstructing an enzyme known as phosphodiesterase type 5 (PDE5). This triggered a spike in the key chemical messenger, cyclic GMP (cGMP).

Next, the scientists saw that cGMP targeted and then trapped a protein responsible for transporting cholesterol, the essential fuel that cancer cells rely on to invade other organs. Deprived of this cholesterol, the cancer cells lost their ability to spread, resulting in significantly fewer metastases.

“We uncovered a new biological pathway and showed how this pathway can be harnessed,” said Erez, who is also a practicing physician and serves as a senior researcher and dean of Weizmann’s Miriam and Aaron Gutwirth Medical School.

However, in the next part of the experiment, the researchers saw that the cancer cells weren’t ready to give up the fight.

Once sildenafil kept away the mobile cholesterol, the cancer cells activated a system to produce more cholesterol on their own. That’s when the scientists gave the cancer cells statins, a well-known drug.

According to Johns Hopkins University, more than 200 million people worldwide take statins to lower their cholesterol levels.

The statins combined with sildenafil worked in tandem, maintaining low cholesterol levels and preventing the cancer from spreading.

Dr. Samah Hayek, senior epidemiologist at Clalit Health Services and a senior lecturer in Tel Aviv University’s Department of Epidemiology and Preventive Medicine, told The Times of Israel that the Weizmann researchers contacted her to check their lab findings against Clalit patient data.

Hayek said the researchers wanted her to investigate what happened to cancer patients who received Viagra 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,” she said. “So that’s where the combination of two different disciplines came together, and we succeeded in answering an important research question.”

According to Dr. Ido Wolf, head of the oncology division at Tel Aviv Medical Center and head of Tel Aviv University’s Medical School, “The study highlights a fascinating and underappreciated aspect of cancer biology.”

Wolf was not involved in the study.

“Metastatic cancer cells critically depend on cholesterol, and disrupting its intracellular trafficking represents a previously unrecognized therapeutic vulnerability,” he explained. “Beyond uncovering this mechanism, the authors support their findings with population-scale real-world clinical data.”

Wolf emphasized that the findings “demonstrate the potential for rapid drug repurposing using widely available, well-established medications such as sildenafil and statins.”

“This is the part of translational science that goes from the lab, from mouse modeling to human modeling,” Hayek said. “We try to translate the science and then give the science to the patients.”

Erez added that she thought the message the research also conveyed “is not just to focus on the cancer mutation and the tumor microenvironment.”

“We need to add the patients to the equation,” she said. “What they eat, their physical activity, and the drugs that they are taking. It’s important to look at patients as a whole organism.”

The war with Iran has been draining for all of us in Israel. But when I heard about a high casualty incident – ballistic missile impacts in Arad and Dimona that left nearly 200 people wounded – I drank a cup of coffee, packed a bag, and headed south.

There, I spoke with Shilgit, the head of an after-school program for underprivileged youth. Standing outside her destroyed center, Shilgit said it was a miracle that no children were hurt and spoke about the community coming together in the hours since.

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