Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer

Jacqueline M. Lafky, Jason A. Wilken, Andre T. Baron, Nita Jane Maihle

Research output: Contribution to journalReview article

150 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)232-265
Number of pages34
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Volume1785
Issue number2
DOIs
StatePublished - Apr 1 2008

Fingerprint

Epidermal Growth Factor Receptor
Ovarian Neoplasms
Ligands
Neoplasms
Therapeutics
Proto-Oncogenes
Gene Amplification
Antineoplastic Agents
Protein-Tyrosine Kinases
Disease-Free Survival
Signal Transduction
Cell Survival
Protein Isoforms
Biomarkers
Cell Proliferation
ErbB Receptors
Clinical Trials
Recurrence
Mutation
Serum

Keywords

  • Amphiregulin
  • Biomarkers
  • EGF family
  • EGF receptor
  • ErbB receptors
  • HER family
  • Heregulins
  • Neuregulins
  • Ovarian cancer
  • Receptor tyrosine kinases
  • Soluble ErbB receptors
  • TGF-α

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

Cite this

Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer. / Lafky, Jacqueline M.; Wilken, Jason A.; Baron, Andre T.; Maihle, Nita Jane.

In: Biochimica et Biophysica Acta - Reviews on Cancer, Vol. 1785, No. 2, 01.04.2008, p. 232-265.

Research output: Contribution to journalReview article

Lafky, Jacqueline M. ; Wilken, Jason A. ; Baron, Andre T. ; Maihle, Nita Jane. / Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer. In: Biochimica et Biophysica Acta - Reviews on Cancer. 2008 ; Vol. 1785, No. 2. pp. 232-265.
@article{7b1f388ff5894809850667dd3ac98815,
title = "Clinical implications of the ErbB/epidermal growth factor (EGF) receptor family and its ligands in ovarian cancer",
abstract = "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.",
keywords = "Amphiregulin, Biomarkers, EGF family, EGF receptor, ErbB receptors, HER family, Heregulins, Neuregulins, Ovarian cancer, Receptor tyrosine kinases, Soluble ErbB receptors, TGF-α",
author = "Lafky, {Jacqueline M.} and Wilken, {Jason A.} and Baron, {Andre T.} and Maihle, {Nita Jane}",
year = "2008",
month = "4",
day = "1",
doi = "10.1016/j.bbcan.2008.01.001",
language = "English (US)",
volume = "1785",
pages = "232--265",
journal = "Biochimica et Biophysica Acta - Reviews on Cancer",
issn = "0304-419X",
publisher = "Elsevier",
number = "2",

}

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 Jane

PY - 2008/4/1

Y1 - 2008/4/1

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

UR - http://www.scopus.com/inward/record.url?scp=41949100690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41949100690&partnerID=8YFLogxK

U2 - 10.1016/j.bbcan.2008.01.001

DO - 10.1016/j.bbcan.2008.01.001

M3 - Review article

C2 - 18291115

AN - SCOPUS:41949100690

VL - 1785

SP - 232

EP - 265

JO - Biochimica et Biophysica Acta - Reviews on Cancer

JF - Biochimica et Biophysica Acta - Reviews on Cancer

SN - 0304-419X

IS - 2

ER -