TY - JOUR
T1 - Cross-talk between the ErbB/HER family and the type I insulin-like growth factor receptor signaling pathway in breast cancer
AU - Jin, Quanri
AU - Esteva, Francisco J.
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - Breast cancers
KW - Human epidermal growth factor receptor
KW - Insulin-like growth factor receptor
KW - Signaling interactions
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U2 - 10.1007/s10911-008-9107-3
DO - 10.1007/s10911-008-9107-3
M3 - Article
C2 - 19034632
AN - SCOPUS:57149142362
SN - 1083-3021
VL - 13
SP - 485
EP - 498
JO - Journal of Mammary Gland Biology and Neoplasia
JF - Journal of Mammary Gland Biology and Neoplasia
IS - 4
ER -