The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC

Gately, K., O'Flaherty, J., Cappuzzo, F., Pirker, R., Kerr, K., & O'Byrne, Kenneth J. (2012) The role of the molecular footprint of EGFR in tailoring treatment decisions in NSCLC. Journal of Clinical Pathology, 65(1), pp. 1-7.

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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/panerb inhibitors. A number of techniques have been employed for genotypic assessment of tumourassociated 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.

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ID Code: 65071
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: epidermal growth factor receptor, erlotinib, gefitinib, molecular marker, protein tyrosine kinase, protein tyrosine kinase inhibitor, somatomedin receptor, cancer cell, cancer relapse, chromosome substitution, disease course, DNA determination, DNA footprinting, drug sensitivity, enzyme activity, exon, gene activation, gene amplification, gene deletion, gene mutation, human, lung non small cell cancer, molecular dynamics, molecularly targeted therapy, outcome assessment, pathogenesis, priority journal, protein expression, review, treatment indication, treatment response, Animals, Antineoplastic Agents, Carcinoma, Non-Small-Cell Lung, DNA Mutational Analysis, Genetic Testing, Humans, Individualized Medicine, Lung Neoplasms, Molecular Targeted Therapy, Mutation, Neoplasm Recurrence, Local, Patient Selection, Protein Kinase Inhibitors, Receptor, Epidermal Growth Factor, Time Factors, Treatment Outcome
DOI: 10.1136/jclinpath-2011-200275
ISSN: 0021-9746
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2012 B M J Group
Deposited On: 04 Dec 2013 01:06
Last Modified: 19 Dec 2013 03:23

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