Cancer Cell International (Mar 2022)

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

  • Aysooda Hosseinzadeh,
  • Parnaz Merikhian,
  • Nazanin Naseri,
  • Mohammad Reza Eisavand,
  • Leila Farahmand

DOI
https://doi.org/10.1186/s12935-022-02523-z
Journal volume & issue
Vol. 22, no. 1
pp. 1 – 14

Abstract

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Abstract 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.

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