Repurposed Heart Drug May Treat Breast Cancer

New research indicates that a drug that improves blood flow to the heart may present a novel treatment option for patients with triple negative breast cancer (TNBC).

Investigators at Houston Methodist Hospital are currently conducting a study to determine whether combining L- NMMA (Tilarginine Acetate) ― a nitric oxide synthase inhibitor ―plus chemotherapy, is a safe and effective treatment for patients with TNBC.

The drug was originally developed to treat patients with cardiogenic shock, which is a condition where circulation to the heart is severely impaired, and the heart does not pump enough blood to the organs. Despite being tested in thousands of patients, the FDA rejected the new drug application because the study did not meet its objectives and endpoints, according to the researchers.

It is now thought that L-NMMA can prevent the body from creating nitric oxide synthase, which can reduce the formation of new tumor blood vessels. By preventing blood vessels from forming, tumor growth and spread is also prevented.

"Tilarginine Acetate (L-NMMA) combined with standard chemotherapy treatment has already proven to be an effective small molecule inhibitor in mice, where we've targeted treatment resistance and metastases," said the study’s principal investigator Angel Rodriguez, MD. "Our initial findings could lay the foundation for developing new therapies for women with triple negative breast cancer, for which prognosis is extremely poor."

Repurposing drugs is a strategy many researchers use to make novel treatments available to patients. Since the cost of research and development is so high, and the process could extend longer than a decade, repurposing a drug that has already been through clinical testing mitigates those unattractive factors.

Identifying potential candidates for cancer drugs among FDA-approved drugs or failed drugs are effective ways to speed up the testing process, and allows the drug to be available quickly.

"Current development of cancer therapeutics is largely based on identifying agents with the ability to control tumor resistant cells and avoid metastasis in solid malignancies," Dr Rodriguez said.

The goal of this new phase 1 study is to determine the maximum tolerated dose, and associated toxicities with a combination of L-NMMA and chemotherapy, according to the researchers. Included in the 20-week study will be 30 patients with locally advanced or metastatic TNBC.

The investigators warn that potential side effects may include increased blood pressure, stroke, and an allergic reaction to the combination therapy.

TNBC is the most aggressive and challenging subtype of breast cancer, since it does not express genes for estrogen receptors, progesterone receptors, and human epidermal growth receptor 2. Due to this lack of expression, patients with TNBC likely will not respond to targeted treatments, which severely limits their options.

By exploring a treatment option that includes a drug that has already been through clinical testing, patients with TNBC may have access to an effective drug therapy that would have otherwise been delayed due to the development process.