VEGF-A 165 family of isoforms as predictive biomarkers in patients with nonsquamous non-small cell lung cancer (NSCLC) treated with bevacizumab
| Autor: | Irene Moreno, Jesús García-Foncillas, Francisco J. Lobo, Ana Leon, Tatiana Hernandez, Jose Ignacio Martin-Valades, Cristina Chamizo, Carmen Laura Auz, Nerea Carvajal, Juan Madoz, Cristina Caramés, Gloria Serrano, Sandra Zazo, Manuel Domine, Nuria Perez-Gonzalez, Federico Rojo |
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| Rok vydání: | 2013 |
| Předmět: |
Gene isoform
Oncology Cancer Research medicine.medical_specialty Bevacizumab business.industry non-small cell lung cancer (NSCLC) medicine.disease Humanized antibody law.invention Vascular endothelial growth factor chemistry.chemical_compound chemistry law Internal medicine Monoclonal medicine Recombinant DNA In patient business medicine.drug |
| Zdroj: | Journal of Clinical Oncology. 31:e19109-e19109 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2013.31.15_suppl.e19109 |
| Popis: | e19109 Background: Bevacizumab is a recombinant monoclonal humanized antibody to vascular endothelial growth factor (VEGF) that improves Time to Progression (TTP) in patients with advanced non-squamous NSCLC in combination with a doublet of platins, but currently no proven predictive markers exist. The VEGF-A 165 splice variant has been described as the most abundant and active isoform in cancer. Exon 8 splice modifications of VEGF 165 generates the VEGF-A 165a family of isoforms, which has a pro-angiogenic effect, and VEGF-A 165b family, with an anti-angiogenic activity. This study is aimed to explore the role of VEGF165a and VEGF165b expression in tumors as predictive biomarkers of efficacy in patients with NSCLC treated with platins plus bevacizumab. Methods: 22 patients were included (20 adenocarcinomas and 2 large cell carcinomas): 5 received carboplatin-taxol-bevacizumab, 14 carboplatin-taxotere-bevacizumab and 3 cisplatin-gemcitabine-bevacizumab. Total RNA was isolated by RNeasy FFPE procedure. VEGF165a and VEGF165b expression was analyzed by RT-qPCR using appropriate specific primers and probes. Individual VEGF165a and VEGF165b family of isoforms expression was calibrated to normal tissue and the ratio between both isoforms was calculated. Results: VEGF165a overexpression was detected in 14 (63.6%) cases and VEGF165b overexpression in 15 (68.2%). Individual overexpression for each family of isoforms was not predictive of benefit to bevacizumab therapy (p=0.933 and 0.166). However, the ratio between VEGF165a and VEGF165b was associated with TTP, correlating a predominant expression of pro-angiogenic VEGF165a with a significant benefit compared with cases with predominant VEGF165b expression (median TTP, 15 vs. 8 months respectively, p=0.005). The expression of both isoforms did not impact on OS (p=0.477). Conclusions: The overexpression of VEGF165a and low expression of VEGF165b family of isoforms correlated with benefit to anti-angiogenic therapy in NSCLC patients, supporting a potential use as predictive biomarkers for bevacizumab treatment in stage IV non-squamous NSCLC. |
| Databáze: | OpenAIRE |
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