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The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC
  1. Kathy Gately1,
  2. John O'Flaherty1,
  3. Frederico Cappuzzo2,
  4. Robert Pirker3,
  5. Keith Kerr4,
  6. Kenneth O'Byrne1
  1. 1Department of Clinical Medicine, Institute of Molecular Medicine, St James's Hospital, Dublin, Ireland
  2. 2Department of Haematology-Oncology, Istituto Clinico Humanitas, Rozzano, Italy
  3. 3Department of Medicine I, Medical University Vienna, Vienna, Austria
  4. 4Department of Pathology, Aberdeen University Medical School, Aberdeen, UK
  1. Correspondence to Professor Dr Kenneth O'Byrne, Hope Directorate, St James's Hospital, PO Box 580, James's Street, Dublin 8, Ireland; kobyrne{at}


The majority of patients with non-small-cell lung cancer (NSCLC) present with advanced disease, with targeted therapies providing some improvement in clinical outcomes. The epidermal growth factor receptor (EGFR) tyrosine kinase (TK) plays an important role in the pathogenesis of NSCLC. Tyrosine kinase inhibitors (TKIs), which target the EGFR TK domain, have proven to be an effective treatment strategy; however, patient responses to treatment vary considerably. Therefore, the identification of patients most likely to respond to treatment is essential to optimise the benefit of TKIs. Tumour-associated activating mutations in EGFR can identify patients with NSCLC who are likely to have a good response to TKIs. Nonetheless, the majority of patients relapse within a year of starting treatment. Studies of tumours at relapse have demonstrated expression of a T790M mutation in exon 20 of the EGFR TK domain in approximately 50% of cases. Although conferring resistance to reversible TKIs, these patients may remain sensitive to new-generation irreversible/pan-erb inhibitors. A number of techniques have been employed for genotypic assessment of tumour-associated DNA to identify EGFR mutations, each of which has advantages and disadvantages. This review presents an overview of the current methodologies used to identify such molecular markers. Recent developments in technology may make the monitoring of changes in patients' tumour genotypes easier in clinical practice, which may enable patients' treatment regimens to be tailored during the course of their disease, potentially leading to improved patient outcomes.

  • epidermal growth factor receptor
  • non-small cell lung cancer
  • tyrosine kinase inhibitor
  • molecular marker
  • molecular oncology
  • molecular pathology
  • lung cancer
  • cardiothoracic pathology
  • tumour biology
  • lung
  • pulmonary pathology
  • airways disease
  • neoplasms
  • oncology

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  • Funding This manuscript was supported by Boehringer Ingelheim. The authors would like to acknowledge the editorial assistance of Ogilvy Healthworld. Boehringer Ingelheim provided financial support to Ogilvy Healthworld for this assistance.

  • Competing interests FC has received speaker's fees from Merck Serono, Roche and AstraZeneca, and honoraria for Advisory Boards from Merck Serono, Roche, Boehringer Ingelheim and AstraZeneca. RP has received speaker's fees and/or honoraria from Roche, AstraZeneca, Boehringer-Ingelheim and Merck Serono. KK has received honoraria and/or consultancy fees from Eli Lilly, Roche-Genentech-OSI, Astra Zeneca, GlaxoSmithKline, Boehringer Ingelheim. KO'B has participated on advisory boards and received speaker's fees from Boehringer Ingelheim, Eli Lilly, Roche-Genetech, AstraZeneca, Amgen, Clovis and Merck-Serono.

  • Provenance and peer review Not commissioned; externally peer reviewed.