TY - JOUR
T1 - Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer
AU - Lafky, Jacqueline M.
AU - Wilken, Jason A.
AU - Baron, Andre T.
AU - Maihle, Nita J.
N1 - Funding Information:
This work has been supported by NIH/NCI and Office of Women's Health Resources grants R01 CA57534 and U01 CA85133, as well as by a Yale University School of Medicine Senior Women in Medicine Professorship to NJM; a grant from the Elsa U Pardee Foundation, a Research Program of Excellence Award from the Ovarian Cancer Research Fund, Inc., and a Ladies Auxiliary to the Veterans of Foreign Wars Cancer Research Postdoctoral Fellowship to JAW; and by the Prospect Creek and Rivkin Foundations. The authors thank Ms. Daniele de Vries and Dr. Yingqun Huang for translation services.
PY - 2008/4
Y1 - 2008/4
N2 - The ERBB or EGF receptor (EGFR) proto-oncogene family, which consists of four structurally-related transmembrane receptors (i.e., EGFR, ErbB2, ErbB3, and ErbB4), plays an etiological role in the molecular pathogenesis of cancer and is a key therapeutic target in many types of cancer, including ovarian cancer. These ErbB/EGF receptor tyrosine kinases play important physiologic roles in cell proliferation, survival, adhesion, motility, invasion, and angiogenesis. It is, therefore, not surprising that gene amplification, genetic mutation, and altered transcription/translation result in aberrant ErbB/EGF receptor expression and/or signal transduction, contributing to the development of malignant transformation. Clinically, the diagnostic, prognostic, and theragnostic significance of any single ErbB receptor and/or ErbB ligand is controversial, but generally, ErbB receptor overexpression has been correlated with poor prognosis and decreased therapeutic responsiveness in ovarian cancer patients. Thus, anticancer agents targeting ErbB/EGF receptors hold great promise for personalized cancer treatment. Yet, challenges remain in designing prospective clinical trials to assess the clinical utility of ErbB receptors and their ligands to diagnose cancer; to predict progression-free and overall survival, therapeutic responsiveness, and disease recurrence; and to monitor treatment responsiveness. Here, we review the tissue expression and serum biomarker studies that have evaluated the diagnostic, prognostic, and theragnostic utility of ErbB/EGF receptors, their circulating soluble isoforms (sEGFR/sErbBs), and their cognate ligands in ovarian cancer patients.
AB - The ERBB or EGF receptor (EGFR) proto-oncogene family, which consists of four structurally-related transmembrane receptors (i.e., EGFR, ErbB2, ErbB3, and ErbB4), plays an etiological role in the molecular pathogenesis of cancer and is a key therapeutic target in many types of cancer, including ovarian cancer. These ErbB/EGF receptor tyrosine kinases play important physiologic roles in cell proliferation, survival, adhesion, motility, invasion, and angiogenesis. It is, therefore, not surprising that gene amplification, genetic mutation, and altered transcription/translation result in aberrant ErbB/EGF receptor expression and/or signal transduction, contributing to the development of malignant transformation. Clinically, the diagnostic, prognostic, and theragnostic significance of any single ErbB receptor and/or ErbB ligand is controversial, but generally, ErbB receptor overexpression has been correlated with poor prognosis and decreased therapeutic responsiveness in ovarian cancer patients. Thus, anticancer agents targeting ErbB/EGF receptors hold great promise for personalized cancer treatment. Yet, challenges remain in designing prospective clinical trials to assess the clinical utility of ErbB receptors and their ligands to diagnose cancer; to predict progression-free and overall survival, therapeutic responsiveness, and disease recurrence; and to monitor treatment responsiveness. Here, we review the tissue expression and serum biomarker studies that have evaluated the diagnostic, prognostic, and theragnostic utility of ErbB/EGF receptors, their circulating soluble isoforms (sEGFR/sErbBs), and their cognate ligands in ovarian cancer patients.
KW - Amphiregulin
KW - Biomarkers
KW - EGF family
KW - EGF receptor
KW - ErbB receptors
KW - HER family
KW - Heregulins
KW - Neuregulins
KW - Ovarian cancer
KW - Receptor tyrosine kinases
KW - Soluble ErbB receptors
KW - TGF-α
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U2 - 10.1016/j.bbcan.2008.01.001
DO - 10.1016/j.bbcan.2008.01.001
M3 - Review article
C2 - 18291115
AN - SCOPUS:41949100690
SN - 0304-419X
VL - 1785
SP - 232
EP - 265
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
IS - 2
ER -