EGFR G796D mutation mediates resistance to osimertinib

Oncotarget. 2017 Jul 25;8(30):49671-49679. doi: 10.18632/oncotarget.17913.

Abstract

Osimertinib is an effective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved in multiple countries and regions for patients with EGFR T790M mutation-positive non-small cell lung cancer (NSCLC). Despite impressive initial tumor responses, development of drug resistance ultimately limits the benefit of this compound. Mechanisms of resistance to osimertinib are just beginning to emerge, such as EGFR C797S and L718Q mutations, BRAF V600E and PIK3CA E545K mutations, as well as ERBB2 and MET amplification. However, a comprehensive view is still missing. In this study, we presented the first case of Chinese NSCLC patient who developed resistance to osimertinib, and discovered de novo EGFR G796D mutation as a potential mechanism. Our findings provided insights into mechanisms of resistance to osimertinib and highlighted tumor heterogeneity and clonal evolution during the development of drug resistance.

Keywords: EGFR; G796D; NSCLC; drug resistance; osimertinib.

Publication types

  • Case Reports

MeSH terms

  • Acrylamides
  • Amino Acid Substitution*
  • Aniline Compounds
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / genetics*
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Middle Aged
  • Mutation*
  • Piperazines / pharmacology*
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Tomography, X-Ray Computed

Substances

  • Acrylamides
  • Aniline Compounds
  • Antineoplastic Agents
  • Piperazines
  • Protein Kinase Inhibitors
  • osimertinib
  • ErbB Receptors