Epidermal growth factor receptor tyrosine kinase inhibitors as anticancer agents

Drugs. 2000;60 Suppl 1:25-32; discussion 41-2. doi: 10.2165/00003495-200060001-00003.


The epidermal growth factor receptor (EGFR)-driven autocrine growth pathway has been implicated in the development and progression of the majority of the most common human epithelial cancers, making the blockade of this growth pathway a promising anticancer therapeutic strategy. Different approaches have been developed to block EGFR activation and/or function in cancer cells. In the past 15 years, various anti-EGFR blocking monoclonal antibodies (MAb), recombinant proteins containing transforming growth factor-alpha (TGFalpha) or EGF fused to toxins, and tyrosine kinase inhibitors (TKIs) have been generated and their biological and potentially therapeutic properties characterised. One of these agents, MAb IMC-C225, a chimeric human-mouse IgG1 MAb, is the first anti-EGFR agent to enter phase II to III clinical trials in patients with cancer. Several small compounds that block the ligand-induced activation of the EGFR tyrosine kinase have been developed. Among these EGFR-TKIs, various quinazoline-derived agents have been synthesised and have shown promising activity as anticancer agents in preclinical models. ZD1839 ('Iressa'), an anilinoquinazoline, is an orally active, selective EGFR-TKI which is currently under clinical evaluation in phase II to III clinical trials in patients with cancer. Preclinical data for ZD1839 strongly support the possibility of potentiating the antitumour activity of conventional chemotherapy with agents that selectively block the EGFR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Oral
  • Antibodies, Monoclonal / therapeutic use
  • Antineoplastic Agents / pharmacology*
  • Disease Progression
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / physiology
  • Gefitinib
  • Humans
  • Ligands
  • Neoplasms / drug therapy*
  • Neoplasms / physiopathology
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / metabolism
  • Quinazolines / pharmacology*
  • Signal Transduction / drug effects
  • Transforming Growth Factor alpha / pharmacology


  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Ligands
  • Quinazolines
  • Transforming Growth Factor alpha
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Gefitinib