The commonly used chemotherapy drug doxorubicin can damage the heart muscle, in some cases leading to heart failure.
In a new study, researchers found that an experimental drug BAI1 can prevent doxorubicin from damaging the heart without lessening its anti-cancer effects.
They suggest that in addition to providing a way to prevent doxorubicin-induced heart damage, a drug like BAI1 might allow doctors to use doxorubicin at higher doses and in combinations with other chemotherapy drugs to treat cancer more effectively.
The research was conducted by led by Albert Einstein College of Medicine scientists.
The incidence of heart damage from doxorubicin is highest among certain groups of cancer patients: older adults, especially those with existing heart disease or risk factors for heart disease; children with hard-to-treat cancers like sarcoma, who often require high doses of the drug; patients who receive multiple doses because of recurrent cancer; and those who have received other cardiotoxic treatments, such as radiation therapy.
In use since 1974, doxorubicin is believed to lead to loss of heart muscle cells through two distinct cell suicide pathways.
So scientists had a single target—BAX—for blocking both types of cell death stemming from the use of doxorubicin.
The researchers developed several drugs, including BAI1, which can bind to BAX and block its transformation.
In the new study, they found that BAI1 works by preventing BAX from converting to its active, lethal form.
The researchers used zebrafish and mice to test whether BAI1 can protect the heart against doxorubicin.
They found the animals did not experience heart damage when doxorubicin and BAI1 were used at the same time.
BAI1 also did not interfere with doxorubicin’s ability to kill cancer cells in breast cancer and leukemia.
The team says the drug may also be able to reduce tissue damage caused by a heart attack and stroke.
Based on the prototype drug BAI1, the researchers continue to work on the development of new drugs and have plans to perform preclinical safety studies to enable testing in human trials.
One author of the study is Richard N. Kitsis, M.D., professor of medicine and of cell biology.
The study is published in the journal Nature Cancer.
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