Tilarginine Acetate, a drug once used to improve blood flow in damaged hearts in thousands of patients, is being investigated as a possible treatment option for triple negative breast cancer (TNBC).

Tilarginine acetate originally was tested in thousands of patients for the treatment of cardiogenic shock, where blood circulation to the heart is severely restricted, and the heart cannot pump enough oxygenated blood to the body’s organs. However, the FDA did not grant approval of Tilarginine acetate to treat cardiogenic shock because the drug did not meet the study objectives and endpoints for the clinical trial.

Now, cancer researchers at Houston Methodist Hospital want to find out whether combining nitric oxide synthase inhibitor Tilarginine acetate (L-NMMA) with standard chemotherapy is a safe treatment option for patients with locally advanced or metastatic TNBC.

Nitric Oxide Synthase Inhibitor Tilarginine Acetate

Dr. Angel Rodriguez, study principal investigator and director of the Triple Negative Breast Cancer Clinic at the Houston Methodist Cancer Center, said;

“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. Our initial findings could lay the foundation for developing new therapies for women with triple negative breast cancer, for which prognosis is extremely poor."

Research suggests that L-NMMA inhibits the body from producing a substance called nitric oxide synthase. By forcing the body to stop making nitric oxide, it also reduces the creation of new tumor blood vessels which feed the cancer stem cells, preventing further tumor growth and the spread of cancer cells.

Using drugs tested previously can be an efficient way to get new treatments to people faster. The cost of making new drugs averages roughly one billion dollars and could take more than a decade to develop.

By identifying strong candidates for cancer treatments among existing FDA-approved drugs or even failed drugs, researchers are finding more effective ways to expedite the treatment process and significantly decrease the amount of time it takes to get medicine to the bedside.

Triple Negative Breast Cancer

About 2.5 million women worldwide live with breast cancer. More than 42,000 new cases of triple negative breast cancer are diagnosed in the United States each year, which is approximately 20 percent of all new diagnoses.

Triple Negative Breast Cancer is the most challenging breast cancer to treat and is distinguished from other breast cancers in that it does not express the genes for estrogen receptors, progesterone receptors, and human epidermal growth receptor 2 (HER2).

The primary goal of this Phase I clinical study is to better understand the maximum tolerated dose and the toxicities associated with this drug combination.

“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,” said Rodriguez.

Approximately 30 patients will participate in this 20-week clinical trial. The study will determine the highest dose of L-NMMA with acceptable side effects when combined with standard chemotherapy for patients who have locally advanced or metastatic triple negative breast cancer.

Image: Anne Weston, LRI, CRUK, Wellcome Images

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