Researchers at VCU Massey Cancer Center have set their sights on a new therapeutic target for an aggressive form of breast cancer with limited treatment options.
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Breast cancer is the second most common cancer in American women, and triple-negative breast cancer (TNBC) is a more aggressive and deadly form of the disease that accounts for 10-15% of all breast tumors. Using a comprehensive, state-of-the-art genomic screening method known as CRISPR/CAS9 screening, scientists were able to identify a specific enzyme called UBA1 that proved to be an ideal therapeutic target. Using a new UBA inhibitor drug called TAK-243, they blocked the cellular function of UBA1 and effectively killed cancer cells in patient-derived breast tumors in mice. Previous research has shown that UBA1 inhibitors can have a positive impact on hematological cancers such as acute myeloid leukemia and chronic myeloid leukemia. This study, recently published in PNAS Nexus, is the first to suggest that UBA1 inhibitors may be effective in TNBC. TAK-243 was recently tested in early phase trials, paving the way for potential testing in TNBC patients. The researchers also determined that the c-MYC gene can be harnessed to cooperate with TAK-243 to initiate a cellular stress response and improve the drug's ability to combat TNBC. This supports the idea that TAK-243 may be effective in TNBC with high c-MYC expression, where c-MYC may serve as a biomarker for drug response.
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