Preclinical Study May Have Found New Treatment Option for Triple-Negative Breast Cancer

Triple negative breast cancer (TNBC) lacks all three of the common receptors found in breast cancer, which makes it harder to treat. The disease also spreads faster and has a worse prognosis. A new study out of Canada may have found a better treatment option for it, though.

In a preclinical study, a team from the Research Institute of the McGill University Health Centre in Montreal uncovered a new targeted combination therapy that reduced tumor growth in metastatic TNBC. The hope is that they can soon test it in human clinical trials. The study was published in the journal Nature Communications.

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Dr. Jean-Jacques Lebrun, the study’s principal investigator and senior scientist in the Cancer Research Program at RI-MUHC, says, “There is no targeted therapy for TNBC. Chemotherapy treatment can even enrich these tumors in cancer stem cells and be detrimental to the patient, as we have shown in a previous study. Filling that huge medical gap was our motivation in conducting this study.”

In most breast cancer cases, a patient has estrogen, progesterone, or HER2 receptors, which allow doctors pathways for treatments. TNBC does not, so the research team used gene editing to look for other pathways that could work.

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After screening the entire human genome through mouse models of TNBC, the team identified approximately 150 genes that could either lead to or prevent tumor formation. Through gene editing, they cut off each’s function in a process called gene knock out. This led them to discover that in TNBC, the tumor pathway MTOR is activated and the tumor suppressor pathway HIPPO is inhibited.

Dr. Meiou Dai, lead author and research associate in the Lebrun Lab at the RI-MUHC, says, “By disrupting the function of all genes, one by one, we found two major pathways that are involved in the regulation of the tumor development. We thought, if we take an existing drug that can block the oncogenic pathway and add one that can promote the tumor suppressor pathway, we could have an effect in terms of blocking cancer formation.”

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The existing drugs they used in the next step were Torin1, which is known to block the MTOR pathway, and verteporfin, which is typically used for a retinal eye disease and can mimic the HIPPO pathway. They mixed the two together, using mathematical models and a pharmacological approach to see if they worked together or independently.

Dr. Lebrun explains, “What we found was beyond our expectations: the two drugs acted in a synergistic manner and efficiently reduced tumor growth in vitro as well as in vivo, using cell- and patient-derived xenograft models of TNBC.”

Researchers say the findings could mean a new approach to prevent tumor formation and reduce tumor size in metastatic TNBC. It also shows the usefulness in gene editing to determine possible treatments for other cancers.

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According to the American Cancer Society, between 10 and 15% of all breast cancer cases are TNBC. It’s most common in women under the age of 40, black women, and those with a BRCA1 mutation.

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