Israeli researchers have identified a biological mechanism by which a widely prescribed, decades-old medication appears to block cancer from spreading to other organs — a finding the team says could open the door to a low-cost treatment built entirely from drugs already sitting on pharmacy shelves.

The peer-reviewed research, conducted at the Weizmann Institute of Science in Rehovot and published in July in the journal Cancer Research, shows that sildenafil interferes with the cholesterol supply that cancer cells depend on when they migrate to new tissue. Deprived of that cholesterol, the cells lost the ability to metastasize.

Dr. Yarden Ariav led the work in the laboratory of Prof. Ayelet Erez, a practicing physician who also serves as dean of Weizmann’s Miriam and Aaron Gutwirth Medical School. The project brought in researchers from Prof. Eytan Ruppin’s lab at the U.S. National Cancer Institute, the Innovation Division of Clalit Health Services — Israel’s largest health provider — and clinicians and scientists at Rabin Medical Center.

Sildenafil was originally developed as a cardiovascular medication because of its effect on blood vessels, and it remains in use for conditions including pulmonary hypertension. It is off-patent, inexpensive and available worldwide, which is a central part of why the Israeli team believes the finding can move quickly from the laboratory toward patients.

How the mechanism works

Using high-resolution cellular imaging, the researchers tracked what happened inside tumor cells in real time. The drug rapidly blocked an enzyme called phosphodiesterase type 5, which in turn produced a surge in a chemical messenger known as cyclic GMP. That messenger trapped the protein responsible for ferrying cholesterol through the cell — effectively cutting off the fuel line metastatic cancer cells rely on to invade other organs. The result was a significant drop in the number of metastases.

The cancer cells did not surrender easily. Once the transported cholesterol was locked away, the tumor cells switched on their own internal production line to manufacture more of it. That is when the researchers added statins, the cholesterol-lowering drugs taken by more than 200 million people globally according to Johns Hopkins University. The two medications worked in tandem, holding cholesterol down and keeping the cancer from spreading.

Laboratory testing concentrated on triple-negative breast cancer, melanoma and lung cancer, using mouse models alongside cultures of cancer cells taken from human patients.

Confirmed against 20 years of patient records

The laboratory results were then tested against real-world data covering roughly five million Clalit members over two decades — an unusual advantage of Israel’s centralized digital health records, which have made the country a repeated testing ground for population-scale medical research.

Dr. Samah Hayek, senior epidemiologist at Clalit Health Services and a senior lecturer in Tel Aviv University’s Department of Epidemiology and Preventive Medicine, examined outcomes for cancer patients who had been taking these medications in the six months before their diagnosis. Survival rates were highest among patients who had been on both sildenafil and statins during that window. Hayek said the epidemiological analysis adjusted for a wide range of confounding factors and still matched what the Weizmann team had observed in the laboratory.

The patient data confirmed the mouse findings for lung, colon and prostate cancer, Erez said.

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 research, said the study identifies a previously unrecognized vulnerability in metastatic disease — the dependence of migrating cancer cells on cholesterol, and the possibility of disrupting how that cholesterol moves inside the cell. He noted that the authors backed the mechanism with population-scale clinical data, and said the findings demonstrate the potential for “rapid drug repurposing” using well-established, widely available medications.

What comes next

Erez said the priority now is a clinical trial testing the approach in women with triple-negative breast cancer, an aggressive form of the disease with limited treatment options. Because both medications are already approved and long established in clinical use, the regulatory path is considerably shorter than for a newly developed compound — the difference between a trial that can begin in the near term and a drug development cycle that typically runs a decade or more and costs billions.

Erez also drew a broader conclusion from the work: that oncology research focused narrowly on tumor mutations and the tumor’s immediate environment is missing part of the picture. Diet, physical activity and the other medications a patient is already taking all belong in the equation, she said, and patients should be evaluated as whole organisms rather than as isolated tumors.

JBizNews Desk | Rehovot, Israel

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