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COLUMBIA, Mo. — All cancers are difficult to treat, and blood cancers are among the trickiest to handle. However, a common high blood pressure drug is helping to weaken leukemia’s defenses against chemotherapy.
Researchers from the University of Missouri School of Medicine are using losartan in a new gene therapy that makes cancer cells more sensitive to the effects of chemo. The new therapy would also protect the heart against toxicity caused by cancer treatments.
Acute myeloid leukemia is one of the most common types of blood cancer among adults. The multiple rounds of chemotherapy a person has to go through disrupts cancer growth, but it also leads to several off-target effects. A major concern is the effect of chemotherapy on the heart, and people undergoing treatment for acute myeloid leukemia are at a higher risk of heart damage.
In an experiment with mice, researchers found that their new targeted gene therapy featuring losartan slowed down cancer growth and increased the mice’s chances of survival from acute myeloid leukemia treatment while avoiding extensive damage to the heart. The results of the animal study are published in the journal Science Translational Medicine.
Methodology
During this study, the research team first had to figure out what leukemia and heart disease have in common. In their search, they discovered a shared target — AGTR1. This gene is a receptor important in cell reproduction. The receptor is overexpressed in the blood cells of people with leukemia. To block the expression of the AGTR1 receptor, the researchers tested the blood pressure medication losartan on diseased mice.
Key Results
Losartan effectively disrupted cancer growth, slowed the spread of cancer cells, and helped mice live longer.
“When we treated mice with the AGTR1 inhibitor losartan, we observed that this commercially available drug shows great promise in reducing AML development while protecting against chemotherapy-induced cardiotoxicity,” says senior study author Xunlei Kang, a professor of Medicine at the University of Missouri School of Medicine, in a media release.
Discussion and Takeaways
While the targeted gene therapy made chemotherapy more effective in mice, researchers caution that the results might be different in humans.
“Mouse models of leukemia differ from human disease in several ways, including differences in the immune system, the bone marrow microenvironment, and responses to treatments,” says lead study author Yi Pan, a PhD student at the University of Missouri School of Medicine. “We will now carefully interpret and validate these findings in human studies to ensure translational relevance.”
The next step for the researchers is to study losartan’s effectiveness in people with acute myeloid leukemia through clinical trials. If the drug is still successful, the FDA will likely approve losartan in a shorter time than most drugs since it is already FDA-approved for other conditions and will not need further research data on the drug.
“This finding shows great potential to both enhance the success of chemotherapy while protecting the heart,” says Kang.
