Prescribed to prevent high blood pressure, losartan may also improve the effectiveness of chemotherapy agents used in the treatment of ovarian cancer.
Antihypertensive commonly prescribed to treat high blood pressure and to prevent strokes in hypertensive people with an increase in the volume of the heart in the left ventricle, losartan would also be effective in the treatment of certain cancers.
This is highlighted by new work carried out by a team of researchers attached to the Massachusetts General Hospital (MGH), in the United States. In an article published online on the Proceedings of the National Academy of Sciences (PNAS) website, they explain that 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 from Massachusetts General Hospital is not at its first work on the properties of losartan. In a previous studythey had identified a similar effect of the anti-hypertensive in animal models of breast and pancreatic cancer, leading to a phase 2 clinical trial which 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, reducing the delivery of drugs and oxygen to tumors,” explains 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 matrix formation. Since levels of an important enzyme in the angiotensin pathway are elevated 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 carried out a series of experiments on two mouse models. They then found that treatment with losartan had reduced extracellular matrix content and solid stress in ovarian tumors. This allowed for increased blood supply, oxygen levels, and drug delivery.
Moreover, by adding losartan to paclitaxel, a drug used in chemotherapy, the researchers found that the antitumor effect of intraperitoneal paclitaxel was greater. Losartan also reduced the development of ascites, ie the accumulation of fluid in the peritoneal cavity, which significantly 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 response or resistance to chemotherapy.
A significant increase in life expectancy
The research team also analyzed the files 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 lived an average of 30 months longer than those receiving other hypertension drugs. .
“The entire class of angiotensin-targeting drugs, including losartan, has been shown to reduce collagen accumulation in fibrotic heart and kidney disease,” Prof. Xu writes. “Losartan is a safe, inexpensive drug that would cost less than a dollar a day while making a significant difference for ovarian cancer patients.”
For scientists, it is now necessary to explore this new therapeutic target for ovarian cancer. The seventh most common female cancer, ovarian cancer is responsible for the death of more than 14,000 women in the United States each year. In France, ovarian cancer affects approximately 4,400 people per year.
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