New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosinekinase inhibitors in lung cancer Journal Article


Authors: Oxnard, G. R.; Arcila, M. E.; Chmielecki, J.; Ladanyi, M.; Miller, V. A.; Pao, W.
Article Title: New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosinekinase inhibitors in lung cancer
Abstract: The management of non-small cell lung carcinoma (NSCLC) has been transformed by the observation that lung adenocarcinomas harboring mutations in epidermal growth factor receptor (EGFR) are uniquely sensitive to EGFR tyrosine kinase inhibitors (TKI). In these patients, acquired resistance to EGFR-TKI develops after a median of 10 to 14 months, at which time the current standard practice is to switch to conventional cytotoxic chemotherapy. Several possible mechanisms for acquired resistance have been identified, the most common being the development of an EGFR T790M gatekeeper mutation in more than 50% of cases. In this review, we discuss recent advances in the understanding of acquired TKI resistance in EGFR-mutant lung cancer and review therapeutic progress with second generation TKIs and combinations of targeted therapies. ©2011 AACR.
Keywords: cancer chemotherapy; unclassified drug; gene mutation; mutation; review; erlotinib; placebo; nonhuman; treatment duration; antineoplastic agents; mutant protein; amino acid substitution; lung non small cell cancer; carcinoma, non-small-cell lung; lung neoplasms; epidermal growth factor receptor; lung cancer; receptor, epidermal growth factor; drug resistance, neoplasm; cell line, tumor; dasatinib; cetuximab; cancer resistance; monoclonal antibody; protein kinase inhibitors; lung adenocarcinoma; add on therapy; gefitinib; vorinostat; heat shock protein 90 inhibitor; fluorine 18; drug sensitivity; pemetrexed; everolimus; epidermal growth factor receptor kinase inhibitor; neratinib; xl 647; retaspimycin; xl 184; crizotinib; afatinib; auy 922; dacomitinib; mm 121
Journal Title: Clinical Cancer Research
Volume: 17
Issue: 17
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2011-09-01
Start Page: 5530
End Page: 5537
Language: English
DOI: 10.1158/1078-0432.ccr-10-2571
PROVIDER: scopus
PMCID: PMC3166976
PUBMED: 21775534
DOI/URL:
Notes: --- - "Export Date: 3 October 2011" - "CODEN: CCREF" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Vincent Miller
    261 Miller
  2. Marc Ladanyi
    863 Ladanyi
  3. Maria Eugenia Arcila
    336 Arcila