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Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors

Abstract

Most patients with non-small-cell lung cancer (NSCLC) present with advanced disease. Current treatment paradigms are shifting from cytotoxic chemotherapies alone to single-agent and combination biological and targeted therapies. As patient responses to these therapies vary, predictive biomarkers will be an important facet of a patient's diagnostic workup in personalized medicine, as there is accumulating evidence that they may enable the prognostication and prediction of therapeutic response. Potential biomarkers for the selection of patients with NSCLC most likely to benefit from epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib, include mutations, gene copy number increase and single-nucleotide polymorphisms of the EGFR gene, EGFR protein expression and oncogenic mutation on the KRAS gene. Many techniques are available to assay for these biomarkers. In this review, we present the current weight of evidence for using these methods as biomarkers for anti-EGFR therapy in patients with NSCLC.

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Acknowledgements

This article was funded by Boehringer Ingelheim Pharmaceuticals Inc. Dr John is an International Association for Study of Lung Cancer (IASLC) Translational Fellow in Lung Cancer Research. Dr Liu is the Alan B Brown Chair in Molecular Genomics, and Dr Tsao is the M Qasim Choksi Chair in Lung Cancer Translational Research.

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John, T., Liu, G. & Tsao, MS. Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors. Oncogene 28 (Suppl 1), S14–S23 (2009). https://doi.org/10.1038/onc.2009.197

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