A brief perspective of drug resistance toward EGFR inhibitors: the crystal structures of EGFRs and their variants

Future Med Chem. 2017 May;9(7):693-704. doi: 10.4155/fmc-2016-0222. Epub 2017 May 15.

Abstract

The EGFR is one of the most popular targets for anticancer therapies and many drugs, such as erlotinib and gefitinib, have got enormous success in clinical treatments of cancer in past decade. However, the efficacy of these agents is often limited because of the quick emergence of drug resistance. Fundamental structure researches of EGFR in recent years have generally elucidated the mechanism of drug resistance. In this review, based on systematic resolution of full structures of EGFR and their variants via single crystal x-ray crystallography, the working and drug resistance mechanism of EGFR-targeted drugs are fully illustrated. Moreover, new strategies for avoiding EGFR drug resistance in cancer treatments are also discussed.

Keywords: EGFR; drug resistance; variants.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Crystallography, X-Ray
  • Drug Resistance, Neoplasm*
  • Epidermal Growth Factor / chemistry
  • Epidermal Growth Factor / metabolism
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / chemistry*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Humans
  • Lung Neoplasms / drug therapy
  • Mutation
  • Protein Domains
  • Protein Kinase Inhibitors / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Epidermal Growth Factor
  • EGFR protein, human
  • ErbB Receptors