Mechanisms of action of EGFR inhibitors

Nicola Normanno, Maria Pergameno, Alessia Iannaccone, Antonella De Luca

Research output: Chapter in Book/Report/Conference proceedingChapter


The EGF receptor (EGFR) is involved in the pathogenesis of human carcinoma. Two classes of EGFR antagonists are currently in clinical use, anti-EGFR monoclonal antibodies (mAbs) and small-molecule EGFR tyrosine kinase inhibitors (TKIs). Anti-EGFR mAbs prevent ligand binding; inhibit receptor activation; induce dimerization, internalization and downregulation of the EGFR; and activate a host immune response. EGFR TKIs directly inhibit tyrosine kinase phosphorylation by physical interaction with either the ATP and/or the enzyme substrate binding sites. Anti-EGFR drugs are extremely active in subgroups of patients whose tumors depend on EGFR for growth and survival. Non-small-cell lung cancer sensitive to EGFR TKIs carry activating mutations of the EGFR. Patients that initially respond to anti-EGFR agents usually become resistant to these drugs. Several different mechanism have been shown to produce acquired resistance to anti-EGFR drugs. Preliminary results suggest that genetic mechanisms of resistance might be lost in the absence of the continued selective pressure of EGFR inhibitor treatment.

Original languageEnglish
Title of host publicationEGFR Inhibitors in Cancer Treatment
PublisherFuture Medicine Ltd.
Number of pages11
ISBN (Print)9781780840260, 9781780841137
Publication statusPublished - Jan 1 2012

ASJC Scopus subject areas

  • Medicine(all)


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