Overview of pre-clinical and clinical studies targeting angiogenesis in pancreatic ductal adenocarcinoma. Issue 1 (10th October 2016)

• Record Type: Journal Article
• Authors: Craven, Kelly E.; Gore, Jesse; Korc, Murray
• Is Part Of: Cancer letters. Volume 381:Issue 1(2016)
• Page Start: 201
• Page End: 210
• Publication Date: 2016-10-10
• Subjects: Pancreatic cancer -- Angiogenesis -- Vascular endothelial growth factor (VEGF); ANGPT angiopoietin -- BRAF serine/threonine-protein kinase B-raf -- CAF cancer associated fibroblast -- Cdkn2a cyclin-dependent kinase inhibitor 2A -- CI confidence interval -- CSF1R macrophage colony-stimulating factor 1 receptor -- DLL4 delta-like protein 4 -- EC endothelial cell -- ECM extracellular matrix -- EGFR epidermal growth factor receptor -- FDA Food and Drug Administration -- FGF fibroblast growth factor -- FGF2 fibroblast growth factor 2 -- FGFR-1 fibroblast growth factor receptor 1 (gene: FGFR1) -- FOLFIRINOX fluorouracil plus leucovorin, irinotecan, and oxaliplatin -- GEMM genetically engineered mouse model -- Gpc1 glypican-1 -- HIF-1α hypoxia inducible factor 1, alpha subunit (gene: HIF1A) -- HR hazard ratio -- HRG heregulin (gene: NRG1) -- HSPG heparan sulfate proteogylycan -- I immune cell -- IHC immunohistochemistry -- IL-8 interleukin-8 (gene: CXCL8) -- KC KrasLSL-G12D/+, Pdx-1-Cre -- KIC KrasLSL-G12D/+, Cdkn2aLoxP/LoxP, Pdx-1-Cre -- KPC KrasLSL-G12D/+, Trp53LSL-R172H/+, Pdx-1-Cre -- Kras Kirsten rat sarcoma viral oncogene homolog -- MVD microvessel density -- NCI National Cancer Institute -- NICD notch intracellular domain -- NIH National Institutes of Health -- NRP1 neuropilin-1 -- ORR objective response rate -- OS overall survival -- PCC pancreatic cancer cell -- PDAC pancreatic ductal adenocarcinoma -- PDGF platelet-derived growth factor -- PDGFR platelet-derived growth factor receptor -- PDGFRB platelet-derived growth factor receptor beta -- PFS progression free survival -- PlGF placenta growth factor (gene: PGF) -- RNA-Seq RNA sequencing -- SCFR mast/stem cell growth factor receptor Kit (gene: KIT) -- TCGA The Cancer Genome Atlas -- TGF-β transforming growth factor beta (gene: TGFB1) -- Trp53 transformation related protein 53 -- VEGF vascular endothelial growth factor -- VEGF-A vascular endothelial growth factor A (gene: VEGFA) -- VEGF-B vascular endothelial growth factor B (gene: VEGFB) -- VEGFA vascular endothelial growth factor A (protein: VEGF-A) -- VEGFR vascular endothelial growth factor receptor -- VEGFR-1 vascular endothelial growth factor receptor 1 (gene: FLT1) -- VEGFR-2 vascular endothelial growth factor receptor 2 (gene: KDR) -- VEGFR-3 vascular endothelial growth factor receptor 3 (gene: FLT4); Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.11.047
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: Pancreatic ductal adenocarcinoma (PDAC) is hypovascular. Vascular endothelial growth factor A (gene: VEGFA) (VEGF-A) is overexpressed in PDAC. Increased VEGF-A or microvessel density is associated with poor patient outcome. Blocking VEGF-A in mouse models reduces tumor volumes and improves survival. Clinical trials targeting angiogenesis elicit marginal survival benefit. Abstract: The importance of angiogenesis in pancreatic ductal adenocarcinoma (PDAC) and its therapeutic potential have been explored in both pre-clinical and clinical studies. Human PDACs overexpress a number of angiogenic factors and their cognate high-affinity receptors, and anti-angiogenic agents reduce tumor volume, metastasis, and microvessel density (MVD), and improve survival in subcutaneous and orthotopic pre-clinical models. Nonetheless, clinical trials using anti-angiogenic therapy have been overwhelmingly unsuccessful. This review will focus on these pre-clinical and clinical studies, the potential reasons for failure in the clinical setting, and ways these shortcomings could be addressed in future investigations of angiogenic mechanisms in PDAC.