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MUC1 is a potential target to overcome trastuzumab resistance in breast cancer therapy

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CANCER CELL INTERNATIONAL
卷 22, 期 1, 页码 -

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BMC
DOI: 10.1186/s12935-022-02523-z

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MUC1; Trastuzumab; HER2; Cancer; Drug Resistance

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This article discusses the resistance mechanisms to trastuzumab in breast cancer and proposes MUC1 as a potential target to overcome this resistance. It has been found that silencing the MUC1-C proto-oncogene can increase the sensitivity of HER2(+) cells to trastuzumab.
Although resistance is its major obstacle in cancer therapy, trastuzumab is the most successful agent in treating epidermal growth factor receptor 2 positive (HER2 +) breast cancer (BC). Some patients show resistance to trastuzumab, and scientists want to circumvent this problem. This review elaborately discusses possible resistance mechanisms to trastuzumab and introduces mucin 1 (MUC1) as a potential target efficient for overcoming such resistance. MUC1 belongs to the mucin family, playing the oncogenic/mitogenic roles in cancer cells and interacting with several other oncogenic receptors and pathways, such as HER2, beta-catenin, NF-kappa B, and estrogen receptor (ER alpha). Besides, it has been established that MUC1- Cytoplasmic Domain (MUC1-CD) accelerates the development of resistance to trastuzumab and that silencing MUC1-C proto-oncogene is associated with increased sensitivity of HER2(+) cells to trastuzumab-induced growth inhibitors. We mention why targeting MUC1 can be useful in overcoming trastuzumab resistance in cancer therapy.

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