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Identification and analysis of in vivo VEGF downstream markers link VEGF pathway activity with efficacy of anti-VEGF therapies.

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Citation: Clinical Cancer Research. 19(13):3681-92, 2013 Jul 1.PMID: 23685835Institution: Washington Cancer InstituteForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Angiogenesis Inhibitors/tu [Therapeutic Use] | *Antineoplastic Agents/tu [Therapeutic Use] | *Neoplasms/dt [Drug Therapy] | *Neoplasms/me [Metabolism] | *Signal Transduction/de [Drug Effects] | *Vascular Endothelial Growth Factor A/ai [Antagonists & Inhibitors] | *Vascular Endothelial Growth Factor A/me [Metabolism] | Angiogenesis Inhibitors/pd [Pharmacology] | Animals | Antibodies, Monoclonal, Humanized/pd [Pharmacology] | Antibodies, Monoclonal, Humanized/tu [Therapeutic Use] | Antineoplastic Agents/pd [Pharmacology] | Disease Models, Animal | Drug Evaluation, Preclinical | Gene Expression Profiling | Gene Expression Regulation, Neoplastic/de [Drug Effects] | Humans | Mice | Neoplasms/ge [Genetics] | Neoplasms/mo [Mortality] | Neovascularization, Pathologic/dt [Drug Therapy] | Neovascularization, Pathologic/ge [Genetics] | Neovascularization, Pathologic/me [Metabolism] | Neuroendocrine Tumors/dt [Drug Therapy] | Neuroendocrine Tumors/ge [Genetics] | Neuroendocrine Tumors/me [Metabolism] | Pancreatic Neoplasms/dt [Drug Therapy] | Pancreatic Neoplasms/ge [Genetics] | Pancreatic Neoplasms/me [Metabolism] | Tumor Markers, Biological/ge [Genetics] | Tumor Markers, Biological/me [Metabolism]Year: 2013 Local holdings: Available online from MWHC library: 1995 - present (after 1 year), Available in print through MWHC library: 1999 - February 2003ISSN:

1078-0432

Name of journal: Clinical cancer research : an official journal of the American Association for Cancer ResearchAbstract: CONCLUSIONS: In this work, we identified surrogate markers (VDV genes) for in vivo VEGF signaling in tumors and showed clinical data supporting a correlation between pretreatment VEGF bioactivity and the subsequent efficacy of anti-VEGF therapy. We propose that VDV genes are candidate biomarkers with the potential to aid the selection of novel indications as well as patients likely to respond to anti-VEGF therapy. The data presented here define a diagnostic biomarker hypothesis based on translational research that warrants further evaluation in additional retrospective and prospective trials. 2013 AACR.EXPERIMENTAL DESIGN: Surrogate markers of VEGF inhibition [VEGF-dependent genes or VEGF-dependent vasculature (VDV)] were identified by profiling gene expression 130224s induced in response to VEGF blockade in preclinical tumor models and in human biopsies from patients treated with anti-VEGF monoclonal antibodies. The potential value of VDV genes as candidate predictive biomarkers was tested by correlating high or low VDV gene expression levels in pretreatment clinical samples with the subsequent clinical efficacy of bevacizumab (anti-VEGF)-containing therapy.PURPOSE: The aim of this study was to identify conserved pharmacodynamic and potential predictive biomarkers of response to anti-VEGF therapy using gene expression profiling in preclinical tumor models and in patients.RESULTS: We show that VDV genes, including direct and more distal VEGF downstream endothelial targets, enable detection of VEGF signaling inhibition in mouse tumor models and human tumor biopsies. Retrospective analyses of clinical trial data indicate that patients with higher VDV expression in pretreatment tumor samples exhibited improved clinical outcome when treated with bevacizumab-containing therapies.All authors: Bais C, Brauer MJ, Chen D, Cheng JH, Chung AS, Clermont AC, Ferrara N, Haley B, Hegde P, James CD, Jubb A, Jurinka SS, Kaminker JS, Koeppen H, Kolumam G, Modrusan Z, Ozawa T, Phillips H, Scherer SJ, Schmidt M, Singh M, Stephan JP, Swain SM, Tam RN, Wu X, Yang SX, Yao J, Yeh RF, Yue P, Zhuang GFiscal year: FY2014Digital Object Identifier:

http://dx.doi.org/10.1158/1078-0432.CCR-12-3635

Date added to catalog: 2014-02-24

Holdings ( 1 )
Title notes ( 6 )

Holdings
Item type	Current library	Collection	Call number	Status	Date due	Barcode
Journal Article	MedStar Authors Catalog	Article	23685835	Available		23685835

Available online from MWHC library: 1995 - present (after 1 year), Available in print through MWHC library: 1999 - February 2003

CONCLUSIONS: In this work, we identified surrogate markers (VDV genes) for in vivo VEGF signaling in tumors and showed clinical data supporting a correlation between pretreatment VEGF bioactivity and the subsequent efficacy of anti-VEGF therapy. We propose that VDV genes are candidate biomarkers with the potential to aid the selection of novel indications as well as patients likely to respond to anti-VEGF therapy. The data presented here define a diagnostic biomarker hypothesis based on translational research that warrants further evaluation in additional retrospective and prospective trials. 2013 AACR.

EXPERIMENTAL DESIGN: Surrogate markers of VEGF inhibition [VEGF-dependent genes or VEGF-dependent vasculature (VDV)] were identified by profiling gene expression 130224s induced in response to VEGF blockade in preclinical tumor models and in human biopsies from patients treated with anti-VEGF monoclonal antibodies. The potential value of VDV genes as candidate predictive biomarkers was tested by correlating high or low VDV gene expression levels in pretreatment clinical samples with the subsequent clinical efficacy of bevacizumab (anti-VEGF)-containing therapy.

PURPOSE: The aim of this study was to identify conserved pharmacodynamic and potential predictive biomarkers of response to anti-VEGF therapy using gene expression profiling in preclinical tumor models and in patients.

RESULTS: We show that VDV genes, including direct and more distal VEGF downstream endothelial targets, enable detection of VEGF signaling inhibition in mouse tumor models and human tumor biopsies. Retrospective analyses of clinical trial data indicate that patients with higher VDV expression in pretreatment tumor samples exhibited improved clinical outcome when treated with bevacizumab-containing therapies.

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