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Review
. 2016 Mar 28;10(Suppl 1):21-30.
doi: 10.4137/CMO.S34537. eCollection 2016.

Mechanisms Behind the Resistance to Trastuzumab in HER2-Amplified Breast Cancer and Strategies to Overcome It

María Luque-Cabal  1 , Paula García-Teijido  2 , Yolanda Fernández-Pérez  1 , Luisa Sánchez-Lorenzo  1 , Isabel Palacio-Vázquez  1
Affiliations
Review

Mechanisms Behind the Resistance to Trastuzumab in HER2-Amplified Breast Cancer and Strategies to Overcome It

María Luque-Cabal et al. Clin Med Insights Oncol. .

Abstract

The introduction of trastuzumab therapy markedly improved the poor prognosis associated with HER2-amplified breast cancers. Despite this, the presence of primary and acquired resistance to trastuzumab treatment remains a significant common challenge. The identification of resistance mechanisms and the incorporation of new drugs that achieve a better blockade of HER family receptors signaling have resulted in improved outcomes. The phosphatidylinositol 3'-kinase/protein kinase B/mammalian target of rapamycin pathway, cross-talk with estrogen receptors, immune response, cell cycle control mechanisms, and other tyrosine kinase receptors such as insulin-like growth factor I receptor are potential pathways involved in trastuzumab resistance. Different therapeutic interventions targeting these pathways are currently under evaluation.

Keywords: HER2 overexpression; biomarker; breast cancer; resistance; trastuzumab.

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Figures

Figure 1
Figure 1
Signal transduction by HER2 dimerization.
Figure 2
Figure 2
Mechanisms of resistance to trastuzumab. Abbreviations: Akt, protein kinase B; Cdk 2/4, cyclin-dependent kinase 2/4; E2, estradiol; ER, estrogen receptor; IGF1R, insulin-like growth factor I receptor; HER, human epidermal growth factor receptor; MAPK, Mitogen-activated protein kinases; mTOR, mammalian target of rapamycin; P, phosphorylation; PI3K, phosphatidylinositol 3′-kinase; PI3Kmut, mutated phosphatidylinositol 3′-kinase; PTEN, phosphatase and tensin homolog.
See this image and copyright information in PMC

References

    1. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–82. - PubMed
    1. Yarden Y. The EGFR family and its ligands in human cancer: signalling mechanisms and therapeutic opportunities. Eur J Cancer. 2001;37(suppl 4):S3–8. - PubMed
    1. Brennan PJ, Kumogai T, Berezov A, Murali R, Greene MI. HER2/Neu: mechanisms of dimerization/oligomerization. Oncogene. 2000;19:6093–101. - PubMed
    1. Hudis CA. Trastuzumab – mechanism of action and use in clinical practice. N Engl J Med. 2007;357(1):39–51. - PubMed
    1. Slamon DJ, Leyland-Jones B, Shak S, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–92. - PubMed