Ovarian cancer: an antihypertensive could improve treatment

Prescribed to prevent high blood pressure, losartan may also improve the effectiveness of chemotherapy agents used in the treatment of ovarian cancer.

An antihypertensive drug commonly prescribed to treat high blood pressure and to prevent stroke in hypertensive patients with increased heart volume in the left ventricle, losartan is also effective in the treatment of certain cancers.

This is highlighted by new work conducted by a team of researchers from the Massachusetts General Hospital (MGH) in the United States. In an article published online on the Proceedings of the National Academy of Sciences (PNAS), they said they discovered that losartan was able to improve the effectiveness of chemotherapy agents used in the treatment of ovarian cancer.

Depletion of the extracellular matrix

The team of researchers at Massachusetts General Hospital is not at its early work on the properties of losartan. In a previous study, they had identified a similar effect of the antihypertensive drug in animal models of breast and pancreatic cancer, leading to a Phase 2 clinical trial that had shown promising results against pancreatic cancer.

“We know that the solid stress imposed by the growth of cancer cells and the extracellular matrix molecules they produce can compress blood vessels, thus reducing the delivery of drugs and oxygen to tumors,” says Prof. Lei Xu, lead author of the study. “The extracellular matrix itself can prevent high molecular weight drugs from entering tumors, and angiotensin signaling contributes to the formation of the matrix.” Because the levels of an important enzyme in the angiotensin pathway are high and associated with poor outcomes in ovarian cancer, we investigated whether the use of losartan to decrease fibrosis could improve outcomes in animal models of ovarian cancer. ”

To find out, the researchers conducted a series of experiments on two murine models. They found that losartan treatment reduced extracellular matrix content and solid stress in ovarian tumors. This has increased blood supply, oxygen levels and drug delivery.

In addition, by adding losartan to paclitaxel, a drug used in chemotherapy, the researchers found that the antitumor effect of intraperitoneal paclitaxel was greater. Losartan has also reduced the development of ascites, which is the accumulation of fluid in the peritoneal cavity, which greatly reduces the quality of life of patients.

Finally, losartan depleted the extracellular matrix by inducing the expression of antifibrotic miRNA molecules, which could be used as biomarkers of chemotherapy response or resistance.

A significant increase in life expectancy

The research team also conducted an analysis of patients treated for ovarian cancer. They found that those who received standard therapy and were also treated for hypertension with losartan or other angiotensin-targeting drugs experienced an average of 30 months longer than those receiving other antihypertensive drugs. .

“The entire class of angiotensin-targeting drugs, including losartan, has been shown to reduce collagen build-up in fibrotic heart and kidney disease,” writes Professor Xu. “Losartan is a safe and inexpensive drug that would cost less than a dollar a day while making a significant difference for patients with ovarian cancer.”

For scientists, it is now necessary to explore this new therapeutic target of ovarian cancer. Seventh most common female cancer, ovarian cancer is responsible each year for the death of more than 14,000 women in the United States.

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