Sep 24, 2013

Epidermal growth factor receptor: pathway, therapies, and pipeline

Clinical Therapeutics
John R Goffin, Kevin Zbuk

Abstract

The epidermal growth factor receptor (EGFR) pathway is important in tumor growth, survival, and metastasis and is now the target of several therapeutic agents. This paper seeks to review the EGFR pathway, the study and use of EGFR-directed agents in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC), and related new drug development. PubMed was searched for English-language articles by MeSH and title terms of EGFR published from 2006 to 2013, using the limits of clinical trials as well as reviews. Reference lists were assessed for relevant articles, and guidelines were searched. Clinicaltrials.gov and meeting abstracts were queried for investigational agents. Eligible papers included those concerning EGFR biology, NSCLC or CRC studies involving EGFR-directed agents, and/or investigational drugs targeting EGFR and/or associated pathways. The activity of oral tyrosine kinase inhibitors (TKIs) against EGFR has improved survival in NSCLC, and these agents particularly effective in cancers with an EGFR mutation. Resistance to TKIs is most commonly related to a second, T790M, mutation, or to MET amplification, with newer agents directed against these mechanisms. Conversely, in CRC, TKIs have been ineffective, whereas mono...Continue Reading

Mentioned in this Paper

Drug Development
ErbB-2 Receptor
Monoclonal Antibodies
Rat Sarcoma
Biochemical Pathway
ERBB3 gene
Protein Kinase Inhibitors
Antineoplastic Agents
Immunohistochemistry
BRAF protein, human

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