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Journal of Mammary Gland Biology and Neoplasia

, Volume 13, Issue 4, pp 485–498 | Cite as

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

  • Quanri Jin
  • Francisco J. Esteva
Article

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.

Keywords

Human epidermal growth factor receptor Insulin-like growth factor receptor Signaling interactions Breast cancers 

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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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  1. 1.Departments of Breast Medical OncologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  2. 2.Departments of Breast Medical Oncology and Molecular and Cellular OncologyThe University of Texas M. D. Anderson Cancer CenterHoustonUSA
  3. 3.Department of Breast Medical Oncology, Unit 1354The University of Texas M. D. Anderson Cancer CenterHoustonUSA

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