EGFR exon-level biomarkers of the response to bevacizumab/erlotinib in non-small cell lung cancer.
Activating epidermal growth factor receptor (EGFR) mutations are recognized biomarkers for patients with metastatic non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). EGFR TKIs can also have activity against NSCLC without EGFR mutations, requiring the identificat...
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2013
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oai:doaj.org-article:df9c71b1c1b54bdabc04d593f01a7ee12021-11-18T08:56:06ZEGFR exon-level biomarkers of the response to bevacizumab/erlotinib in non-small cell lung cancer.1932-620310.1371/journal.pone.0072966https://doaj.org/article/df9c71b1c1b54bdabc04d593f01a7ee12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24039832/?tool=EBIhttps://doaj.org/toc/1932-6203Activating epidermal growth factor receptor (EGFR) mutations are recognized biomarkers for patients with metastatic non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). EGFR TKIs can also have activity against NSCLC without EGFR mutations, requiring the identification of additional relevant biomarkers. Previous studies on tumor EGFR protein levels and EGFR gene copy number revealed inconsistent results. The aim of the study was to identify novel biomarkers of the response to TKIs in NSCLC by investigating whole genome expression at the exon-level. We used exon arrays and clinical samples from a previous trial (SAKK19/05) to investigate the expression variations at the exon-level of 3 genes potentially playing a key role in modulating treatment response: EGFR, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and vascular endothelial growth factor (VEGFA). We identified the expression of EGFR exon 18 as a new predictive marker for patients with untreated metastatic NSCLC treated with bevacizumab and erlotinib in the first line setting. The overexpression of EGFR exon 18 in tumor was significantly associated with tumor shrinkage, independently of EGFR mutation status. A similar significant association could be found in blood samples. In conclusion, exonic EGFR expression particularly in exon 18 was found to be a relevant predictive biomarker for response to bevacizumab and erlotinib. Based on these results, we propose a new model of EGFR testing in tumor and blood.Florent BatySacha RothschildMartin FrühDaniel BetticherCornelia DrögeRichard CathomasDaniel RauchOliver GautschiLukas BubendorfSusanne CroweFrancesco ZappaMiklos PlessMartin BrutscheSwiss Group for Clinical Cancer ResearchPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e72966 (2013) |
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DOAJ |
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DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Florent Baty Sacha Rothschild Martin Früh Daniel Betticher Cornelia Dröge Richard Cathomas Daniel Rauch Oliver Gautschi Lukas Bubendorf Susanne Crowe Francesco Zappa Miklos Pless Martin Brutsche Swiss Group for Clinical Cancer Research EGFR exon-level biomarkers of the response to bevacizumab/erlotinib in non-small cell lung cancer. |
| description |
Activating epidermal growth factor receptor (EGFR) mutations are recognized biomarkers for patients with metastatic non-small cell lung cancer (NSCLC) treated with EGFR tyrosine kinase inhibitors (TKIs). EGFR TKIs can also have activity against NSCLC without EGFR mutations, requiring the identification of additional relevant biomarkers. Previous studies on tumor EGFR protein levels and EGFR gene copy number revealed inconsistent results. The aim of the study was to identify novel biomarkers of the response to TKIs in NSCLC by investigating whole genome expression at the exon-level. We used exon arrays and clinical samples from a previous trial (SAKK19/05) to investigate the expression variations at the exon-level of 3 genes potentially playing a key role in modulating treatment response: EGFR, V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and vascular endothelial growth factor (VEGFA). We identified the expression of EGFR exon 18 as a new predictive marker for patients with untreated metastatic NSCLC treated with bevacizumab and erlotinib in the first line setting. The overexpression of EGFR exon 18 in tumor was significantly associated with tumor shrinkage, independently of EGFR mutation status. A similar significant association could be found in blood samples. In conclusion, exonic EGFR expression particularly in exon 18 was found to be a relevant predictive biomarker for response to bevacizumab and erlotinib. Based on these results, we propose a new model of EGFR testing in tumor and blood. |
| format |
article |
| author |
Florent Baty Sacha Rothschild Martin Früh Daniel Betticher Cornelia Dröge Richard Cathomas Daniel Rauch Oliver Gautschi Lukas Bubendorf Susanne Crowe Francesco Zappa Miklos Pless Martin Brutsche Swiss Group for Clinical Cancer Research |
| author_facet |
Florent Baty Sacha Rothschild Martin Früh Daniel Betticher Cornelia Dröge Richard Cathomas Daniel Rauch Oliver Gautschi Lukas Bubendorf Susanne Crowe Francesco Zappa Miklos Pless Martin Brutsche Swiss Group for Clinical Cancer Research |
| author_sort |
Florent Baty |
| title |
EGFR exon-level biomarkers of the response to bevacizumab/erlotinib in non-small cell lung cancer. |
| title_short |
EGFR exon-level biomarkers of the response to bevacizumab/erlotinib in non-small cell lung cancer. |
| title_full |
EGFR exon-level biomarkers of the response to bevacizumab/erlotinib in non-small cell lung cancer. |
| title_fullStr |
EGFR exon-level biomarkers of the response to bevacizumab/erlotinib in non-small cell lung cancer. |
| title_full_unstemmed |
EGFR exon-level biomarkers of the response to bevacizumab/erlotinib in non-small cell lung cancer. |
| title_sort |
egfr exon-level biomarkers of the response to bevacizumab/erlotinib in non-small cell lung cancer. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/df9c71b1c1b54bdabc04d593f01a7ee1 |
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