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Mechanisms of Action and Resistance of Trastuzumab in Breast Cancer

  • Chapter
  • First Online:
Resistance to Anti-Cancer Therapeutics Targeting Receptor Tyrosine Kinases and Downstream Pathways

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((RTACT,volume 15))

  • 740 Accesses

Abstract

Breast cancer affects approximately 1 in 8 women. It is estimated that over 252,710 women in the United States will be diagnosed with breast cancer in 2017. Breast cancer-related deaths have declined over the last two decades as a result of early detection and improved treatment, particularly targeted therapies, such as trastuzumab that targets human epidermal growth factor receptor 2 (HER2), which is frequently overexpressed in breast cancer. However, resistance to trastuzumab, either de novo or acquired resistance, presents a major clinical challenge. Here, we summarize the mechanisms of action and resistance of trastuzumab in breast cancer and discuss potential strategies to overcome resistance.

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Abbreviations

ADAM10:

A disintegrin and metalloproteinase domain-containing protein 10

ADC:

Antibody-drug conjugate

ADCC:

Antibody-mediated cellular toxicity

AMPK:

Adenosine monophosphate (AMP)-activated protein kinase

CTF:

Carboxy terminal fragment

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

ECD:

Extracellular domain

EGFR:

Epidermal growth factor receptor

EphA2:

Ephrin receptor A2

HER2:

Human epidermal growth factor receptor 2

HGF:

Hepatocyte growth factor

IGF-1:

Insulin growth factor-1

IGF-1R:

Insulin-like growth factor receptor 1

IGF-2:

Insulin growth factor-2

IHC:

Immunohistochemistry

JAK:

Janus-activated kinase

MAPK:

Mitogen-activated protein kinase

MDM2:

Murine double minute 2

MUC4:

Glycoprotein mucin-4

NK:

Natural killer

NSCLC:

Non-small cell lung cancer

PD-1:

Programmed death-1

PD-L1:

Programmed death ligand-1

PI3K:

Phosphatidylinositol 3-kinase

PIP2 :

Phosphatidylinositol-4,5-bisphosphate

PIP3 :

Phosphatidyl-inositol-3,4,5-trisphosphate

PLCγ:

Phospholipase Cγ

PTEN:

Phosphatase and tensin homologue

STAT:

Signal transducer and activator of transcription

T-DM1:

Ado-trastuzumab emtansine

TKI:

Tyrosine kinase inhibitor

TNFα:

Tumor necrosis factor α

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Acknowledgments

The work was supported by the following grants: National Institutes of Health (CCSG CA016672); Cancer Prevention & Research Institutes of Texas (RP160710 and RP150245); National Breast Cancer Foundation, Inc.; Breast Cancer Research Foundation; Patel Memorial Breast Cancer Endowment Fund; The University of Texas MD Anderson-China Medical University and Hospital Sister Institution Fund; Ministry of Science and Technology, International Research-intensive Centers of Excellence in Taiwan (I-RiCE; MOST 106-2911-I-002-302); Ministry of Health and Welfare, China Medical University Hospital Cancer Research Center of Excellence (MOHW106-TDU-B-212-144003); and Center for Biological Pathways.

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Authors and Affiliations

  1. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Jennifer L. Hsu & Mien-Chie Hung

  2. Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, China Medical University, Taichung, 404, Taiwan

    Jennifer L. Hsu & Mien-Chie Hung

  3. Department of Biotechnology, Asia University, Taichung, 413, Taiwan

    Jennifer L. Hsu & Mien-Chie Hung

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  1. Jennifer L. Hsu
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  2. Mien-Chie Hung
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Correspondence to Mien-Chie Hung .

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  1. Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

    Yosef Yarden

  2. Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Beer-Sheeva, Israel

    Moshe Elkabets

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Hsu, J.L., Hung, MC. (2018). Mechanisms of Action and Resistance of Trastuzumab in Breast Cancer. In: Yarden, Y., Elkabets, M. (eds) Resistance to Anti-Cancer Therapeutics Targeting Receptor Tyrosine Kinases and Downstream Pathways. Resistance to Targeted Anti-Cancer Therapeutics, vol 15. Springer, Cham. https://doi.org/10.1007/978-3-319-67932-7_3

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