ErbB-targeted therapeutic approaches in human cancer

Research output: Contribution to journalReview article

189 Citations (Scopus)

Abstract

The overexpression and aberrant function of the epidermal growth factor receptor (EGFR, erbB1, HER1) and its ligands and coreceptors in a wide spectrum of epithelial cancers have provided a rationale for targeting this signaling network with novel treatment approaches. Several antireceptor therapeutic strategies have been pursued, but two stand ahead in their clinical development. One approach has been the generation of small molecules that compete with adenosine triphosphate (ATP) for binding to the receptor's kinase pocket, thus blocking receptor activation and the transduction of postreceptor signals. The second approach utilizes humanized monoclonal antibodies generated against the receptor's ligand-binding extracellular domain. These antibodies block binding of receptor-activating ligands and, in some cases, can induce receptor endocytosis and downregulation. Clinical studies already suggest that both of these approaches, either alone or in combination with standard anticancer therapies, are well tolerated and can induce clinical responses and tumor stabilization in a variety of common carcinomas.

Original languageEnglish (US)
Pages (from-to)122-130
Number of pages9
JournalExperimental Cell Research
Volume284
Issue number1
DOIs
StatePublished - Mar 10 2003

Fingerprint

Ligands
Antibodies, Monoclonal, Humanized
Neoplasms
Endocytosis
Epidermal Growth Factor Receptor
Signal Transduction
Phosphotransferases
Therapeutics
Down-Regulation
Adenosine Triphosphate
Carcinoma
Antibodies
Clinical Studies

ASJC Scopus subject areas

  • Cell Biology

Cite this

ErbB-targeted therapeutic approaches in human cancer. / Arteaga, Carlos L.

In: Experimental Cell Research, Vol. 284, No. 1, 10.03.2003, p. 122-130.

Research output: Contribution to journalReview article

@article{5bf51ed945104e779b2cbf5d1ad2cbc9,
title = "ErbB-targeted therapeutic approaches in human cancer",
abstract = "The overexpression and aberrant function of the epidermal growth factor receptor (EGFR, erbB1, HER1) and its ligands and coreceptors in a wide spectrum of epithelial cancers have provided a rationale for targeting this signaling network with novel treatment approaches. Several antireceptor therapeutic strategies have been pursued, but two stand ahead in their clinical development. One approach has been the generation of small molecules that compete with adenosine triphosphate (ATP) for binding to the receptor's kinase pocket, thus blocking receptor activation and the transduction of postreceptor signals. The second approach utilizes humanized monoclonal antibodies generated against the receptor's ligand-binding extracellular domain. These antibodies block binding of receptor-activating ligands and, in some cases, can induce receptor endocytosis and downregulation. Clinical studies already suggest that both of these approaches, either alone or in combination with standard anticancer therapies, are well tolerated and can induce clinical responses and tumor stabilization in a variety of common carcinomas.",
author = "Arteaga, {Carlos L.}",
year = "2003",
month = "3",
day = "10",
doi = "10.1016/S0014-4827(02)00104-0",
language = "English (US)",
volume = "284",
pages = "122--130",
journal = "Experimental Cell Research",
issn = "0014-4827",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - ErbB-targeted therapeutic approaches in human cancer

AU - Arteaga, Carlos L.

PY - 2003/3/10

Y1 - 2003/3/10

N2 - The overexpression and aberrant function of the epidermal growth factor receptor (EGFR, erbB1, HER1) and its ligands and coreceptors in a wide spectrum of epithelial cancers have provided a rationale for targeting this signaling network with novel treatment approaches. Several antireceptor therapeutic strategies have been pursued, but two stand ahead in their clinical development. One approach has been the generation of small molecules that compete with adenosine triphosphate (ATP) for binding to the receptor's kinase pocket, thus blocking receptor activation and the transduction of postreceptor signals. The second approach utilizes humanized monoclonal antibodies generated against the receptor's ligand-binding extracellular domain. These antibodies block binding of receptor-activating ligands and, in some cases, can induce receptor endocytosis and downregulation. Clinical studies already suggest that both of these approaches, either alone or in combination with standard anticancer therapies, are well tolerated and can induce clinical responses and tumor stabilization in a variety of common carcinomas.

AB - The overexpression and aberrant function of the epidermal growth factor receptor (EGFR, erbB1, HER1) and its ligands and coreceptors in a wide spectrum of epithelial cancers have provided a rationale for targeting this signaling network with novel treatment approaches. Several antireceptor therapeutic strategies have been pursued, but two stand ahead in their clinical development. One approach has been the generation of small molecules that compete with adenosine triphosphate (ATP) for binding to the receptor's kinase pocket, thus blocking receptor activation and the transduction of postreceptor signals. The second approach utilizes humanized monoclonal antibodies generated against the receptor's ligand-binding extracellular domain. These antibodies block binding of receptor-activating ligands and, in some cases, can induce receptor endocytosis and downregulation. Clinical studies already suggest that both of these approaches, either alone or in combination with standard anticancer therapies, are well tolerated and can induce clinical responses and tumor stabilization in a variety of common carcinomas.

UR - http://www.scopus.com/inward/record.url?scp=0037429652&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037429652&partnerID=8YFLogxK

U2 - 10.1016/S0014-4827(02)00104-0

DO - 10.1016/S0014-4827(02)00104-0

M3 - Review article

C2 - 12648471

AN - SCOPUS:0037429652

VL - 284

SP - 122

EP - 130

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 1

ER -