Hosseinzadeh Aysooda, Merikhian Parnaz, Naseri Nazanin, Eisavand Mohammad Reza, Farahmand Leila
Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, South Gandi, Vanak Squar, 1517964311, Tehran, Iran.
Cancer Cell Int. 2022 Mar 5;22(1):110. doi: 10.1186/s12935-022-02523-z.
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, β-catenin, NF-κB, and estrogen receptor (ERα). 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.
尽管耐药性是癌症治疗中的主要障碍，但曲妥珠单抗是治疗表皮生长因子受体2阳性（HER2+）乳腺癌（BC）最成功的药物。一些患者对曲妥珠单抗表现出耐药性，科学家们希望解决这个问题。这篇综述详细讨论了曲妥珠单抗可能的耐药机制，并介绍了粘蛋白1（MUC1）作为克服这种耐药性的潜在有效靶点。MUC1属于粘蛋白家族，在癌细胞中发挥致癌/促有丝分裂作用，并与其他几种致癌受体和信号通路相互作用，如HER2、β-连环蛋白、核因子κB和雌激素受体（ERα）。此外，已经证实MUC1-细胞质结构域（MUC1-CD）会加速对曲妥珠单抗的耐药性发展，而沉默MUC1-C原癌基因与HER2细胞对曲妥珠单抗诱导的生长抑制剂敏感性增加有关。我们阐述了为何靶向MUC1在癌症治疗中有助于克服曲妥珠单抗耐药性。
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