Resistance to gefitinib

Int J Clin Oncol. 2006 Dec;11(6):487-91. doi: 10.1007/s10147-006-0609-y. Epub 2006 Dec 25.


Subsets of patients with non-small cell lung cancer (NSCLC) who carry somatic mutations in the epidermal growth factor receptor (EGFR) have responded remarkably well to a tyrosine kinase inhibitor (TKI), gefitinib. Despite the dramatic response to this inhibitor, most patients nevertheless ultimately have a relapse. We herein report a case of advanced NSCLC in a patient carrying mutated EGFR (delE746-A750) who had a relapse after dramatic improvement by gefitinib treatment. The DNA sequence of the EGFR gene in a tumor biopsy specimen obtained from the relapse site revealed the presence of a second point mutation, resulting in a threonine-to-methionine amino acid substitution at position 790 of EGFR, which could not be detected in the tumor specimen taken before the treatment. Screening subjects with EGFR mutations therefore allows us to identify patients who can be successfully treated with gefitinib. Such observations should also help us in the search for more effective therapies against a specific subset of NSCLC.

Publication types

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

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Gefitinib
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / pathology
  • Point Mutation
  • Quinazolines / therapeutic use*


  • Antineoplastic Agents
  • Quinazolines
  • ErbB Receptors
  • Gefitinib