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.
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.
John
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University Health Network, Princess Margaret Hospital Site, Ontario Cancer Institute, University of Toronto, Toronto, Ontario, Canada.
Liu
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G
Tsao
M-S
MS
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D018628:Gene Dosage; D005819:Genetic Markers; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D005819:Genetic Markers; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors