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Review
. 2022 Jul 13;9(1):39.
doi: 10.1186/s40779-022-00401-3.

The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer

Zaid Sirhan  1 , Anita Thyagarajan  1 , Ravi P Sahu  2
Affiliations
Review

The efficacy of tucatinib-based therapeutic approaches for HER2-positive breast cancer

Zaid Sirhan et al. Mil Med Res. .

Abstract

Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in approximately 15-20% of breast cancer cases. HER2 is a member of the epidermal growth factor receptor (EGFR) family with tyrosinase kinase activity, and its overexpression is linked to poor prognosis and shorter progression-free survival (PFS) and overall survival (OS). Among various treatment options, HER2-targeting monoclonal antibodies and tyrosine kinase inhibitors (TKIs) have mostly been applied in recent decades to treat HER2-positive (HER2+) breast cancer patients. Although positive clinical outcomes were documented in both advanced disease and neoadjuvant settings, the development of resistance mechanisms to such approaches has been one of the major challenges with the continuous usage of these drugs. In addition, patients who experience disease progression after treatment with multiple HER2-targeted therapies often have limited treatment options. The Food and Drug Administration (FDA) has recently approved a new TKI (i.e., tucatinib) for use in combination with immunotherapy and/or chemotherapeutic agents for the treatment of advanced-stage/metastatic HER2+ breast cancer. This review highlights recent updates on the efficacy of tucatinib-based therapeutic approaches in experimental models as well as in the clinical settings of HER2+ breast cancer.

Keywords: Breast cancer; HER2-positive (HER2+); Immunotherapy; Targeted therapy; Tucatinib.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Mechanisms of HER2 internalization and recycling by trastuzumab mediated via different processes resulting in endocytosis and subsequent degradation/recycling. The mechanism of action of tucatinib is mediated via inhibition of HER2 and HER3 phosphorylation, resulting in blockade of the downstream MAPK and AKT signaling pathways and leading to decreased cell proliferation. HER2/3/4 human epidermal growth factor receptor 2/3/4, EGFR epidermal growth factor receptor, MAPK mitogen-activated protein kinase, PI3K phosphatidylinositol 3-kinase
See this image and copyright information in PMC

References

    1. DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, et al. Breast cancer statistics, 2019. CA Cancer J Clin. 2019;69(6):438–451. doi: 10.3322/caac.21583. - DOI - PubMed
    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. doi: 10.3322/caac.21590. - DOI - PubMed
    1. DeSantis CE, Miller KD, Goding Sauer A, Jemal A, Siegel RL. Cancer statistics for African Americans, 2019. CA Cancer J Clin. 2019;69(3):211–233. doi: 10.3322/caac.21555. - DOI - PubMed
    1. Feng Y, Spezia M, Huang S, Yuan C, Zeng Z, Zhang L, et al. Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis. 2018;5(2):77–106. doi: 10.1016/j.gendis.2018.05.001. - DOI - PMC - PubMed
    1. Yeo SK, Guan JL. Breast cancer: Multiple subtypes within a tumor? Trends Cancer. 2017;3(11):753–760. doi: 10.1016/j.trecan.2017.09.001. - DOI - PMC - PubMed