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Semin Radiat Oncol. 2001 Oct;11(4):281-9.

Radiation response modification following molecular inhibition of epidermal growth factor receptor signaling.

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1
Department of Human Oncology, University of Wisconsin Medical School and Comprehensive Cancer Center, Madison, WI 53792, USA.

Abstract

The epidermal growth factor receptor (EGFR) has emerged as a central molecular target for modulation in cancer therapeutics. The correlation between overexpression of EGFR and clinically aggressive malignant disease renders EGFR a promising therapy target for many epithelial tumors, which represent approximately two thirds of all human cancers. Although the initial impetus for examining EGFR signal interruption as an anticancer strategy involved proliferative growth inhibition, more recent studies now confirm the capacity of EGFR down-regulation to modify apoptosis, invasion capacity, angiogenesis, DNA damage repair, and cellular response to radiation and selected chemotherapy agents. The favorable interaction profile for EGFR blocking agents combined with radiation and/or chemotherapy has stimulated clinical trials in diverse anatomic sites including head and neck, colorectal, pancreas, and lung. Among the most well studied and promising current agents for EGFR signal modulation are C225 and ZD1839. C225 is a chimeric monoclonal antibody to the EGFR (extracellular domain), whereas ZD1839 is a selective inhibitor of the EGFR-tyrosine kinase (cytoplasmic domain). The spectrum of cellular and biological effects that follow molecular blockade of the EGFR is enlarging and reflect the central role of this receptor in regulating epithelial cell behavior. Molecular inhibition of EGFR signaling in combination with radiation represents a highly promising investigational arena. A preview of current translational research efforts and early clinical trials focused primarily on radiation interaction is provided herein.

PMID:
11677653
[Indexed for MEDLINE]

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