- Losartan treatment reduced extracellular matrix content and solid stress in ovarian tumors, increasing blood supply, oxygen levels and drug delivery;
- A mathematical model based on tumor physiology predicts that adding losartan to both low- and high-molecular-weight cancer therapies, delivered either intravenously or intraperitoneally, could improve outcomes;
- Adding losartan to treatment with the chemotherapy drug paclitaxel enhanced the antitumor effect of intraperitoneal paclitaxel and also reduced the development of ascites, accumulations of fluid in the abdomen that significantly reduce patients’ quality of life;
- Losartan depleted the extracellular matrix by inducing the expression of antifibrotic miRNA molecules, which could be used as biomarkers for response or resistance to chemotherapy;
Antihypertension Drug Losartan May Improve Treatment of Ovarian Cancer
January 15, 2019 5:00 pm
The following article is provided by The Clearity Foundation to support women with ovarian cancer and their families. Learn more about The Clearity Foundation and the services we provide directly to women as they make treatment decisions and navigate emotional impacts of their diagnosis.
A new study from a Massachusetts General Hospital (MGH) research team has found that the hypertension drug losartan, which targets the angiotensin signaling pathway, may improve the effectiveness of chemotherapy agents used to treat ovarian cancer. Previous research from the same team identified a similar effect for losartan in animal models of breast and pancreatic cancer, leading to a phase 2 clinical trial that had promising results against pancreatic cancer.
“We know that solid stress imposed by growing cancer cells and the extracellular matrix molecules they produce can compress blood vessels, reducing delivery of drugs and oxygen to tumors,” says Lei Xu, PhD, of the Steele Laboratories for Tumor Biology in the MGH Department of Radiation Oncology, co-senior author of the report published online in PNAS. “The extracellular matrix itself can keep high-molecular-weight drugs from penetrating 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 use of losartan to decrease fibrosis could improve outcomes in animal models of ovarian cancer.”
In a series of experiments in two mouse models the investigators found the following: