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Cross-Talk Between the ErbB/HER Family and the Type I Insulin-Like Growth Factor Receptor Signaling Pathway in Breast Cancer

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Abstract

Understanding the molecular mechanisms involved in tumorigenesis and their influence on clinical outcome is providing specific molecular markers for targeted therapy. Activation of tyrosine kinase receptors from the human epidermal growth factor receptor family (EGFR, HER2, HER3, HER4) and the insulin-like growth factor receptor I (IGF-IR) plays a key role in the initiation and progression of breast cancer. HER2 overexpression is a validated therapeutic target, as shown by the clinical efficacy of trastuzumab and lapatinib. However, only 25–30% of patients with HER2-overexpressing tumors respond to single-agent trastuzumab or lapatinib, and resistance develops even in responding patients. Therefore, to optimize therapeutic efficacy, it is urgent to elucidate the complex network of signaling pathways that develop in breast cancer cells. Signaling interactions have been reported between ErbB/HER family members and IGF-IR. As increased IGF-IR signaling has been implicated in trastuzumab resistance, agents targeting HER2, and IGF-IR could be potential therapeutic tools in breast cancers that develop resistance to HER2-directed therapy.

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Abbreviations

EGFR:

Epidermal growth factor receptor

ER:

Estrogen receptor

IGFBPs:

Insulin-like growth factor binding proteins

IGF-IR:

Type I insulin-like growth factor receptor

IR:

Insulin receptor

MAPK:

Mitogen-activated protein kinase

PI-3K:

Phosphatidylinositol-3-kinase

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Authors and Affiliations

  1. Departments of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Quanri Jin

  2. Departments of Breast Medical Oncology and Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Francisco J. Esteva

  3. Department of Breast Medical Oncology, Unit 1354, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030-4009, USA

    Francisco J. Esteva

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  1. Quanri Jin
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Jin, Q., Esteva, F.J. Cross-Talk Between the ErbB/HER Family and the Type I Insulin-Like Growth Factor Receptor Signaling Pathway in Breast Cancer. J Mammary Gland Biol Neoplasia 13, 485–498 (2008). https://doi.org/10.1007/s10911-008-9107-3

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