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Novel Drug Combination Can Target Triple-Negative Breast Cancer for Treatment
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Novel Drug Combination Can Target Triple-Negative Breast Cancer for Treatment
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In a phase 1/2 clinical trial, Houston Methodist researchers paired a conventional chemotherapy drug with L-NMMA to successfully target triple-negative breast cancer.
A recently published report on a phase 1/2 clinical trial conducted in Houston Methodist could offer renewed hope to patients with triple-negative breast cancer.  
In a new study published in the journal Science Translational Medicine, the investigators paired, for the first time, an antimitotic medication with a nitric oxide synthase inhibitor (L-NMMA), a drug previously studied for managing cardiogenic shock, to treat the aggressive cancer. With this formulation, patented by Houston Methodist, the researchers reported that the patients enrolled in their study had an overall response rate of 45%, with 16.7% of them achieving a complete response.
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Jenny Chang, MD
"It's an exciting new target, and it's also very nontoxic," said Jenny Chang, MD, the Emily Herrmann Chair in Cancer Research and director of the Dr. Mary and Ron Neal Cancer Center. "I think this novel target has great potential for not just breast cancer therapy but also for creating a new generation of drugs for treating other cancers as well."
Chang and her team conducted a phase 1/2 clinical trial to test the efficacy and toxicity of different doses of the combination of taxane and L-NMMA in treating patients with metastatic and locally advanced triple-negative breast cancers. The researchers found that the drug was well-tolerated, with only 21% of patients experiencing adverse effects that were largely attributed to taxane. Patients with locally advanced breast cancer, who were unresponsive to chemotherapy before the clinical trials, were the most responsive to treatment (81% response rate), with 27% showing no cancer at surgery. On the other hand, patients with metastatic breast cancer had a response rate of 15.4%.
Metastatic
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15%
16%
46%
23%
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Locally Advanced
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9%
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46%
45%
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Treatment Failure
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Partial Response
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Stable Disease
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Progressive Disease
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Complete Response
Efficacy of L-NMMA and taxane combination therapy on patients with triple-negative breast cancer (13 metastatic; 11 locally advanced) in the phase 2 trial.
The team also found that the immune cell milieu of patients who responded to the treatment was different from those who did not. With this information, Chang speculated that the next phase of the study may include patient blood testing early in the treatment to quickly identify those who are responsive to the therapy (based on their immune profiles) and spare those who are not. The researchers also plan to investigate the efficacy of their L-NMMA-based drug for different subtypes of triple-negative breast cancer.
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