Overview of pre-clinical and clinical studies targeting angiogenesis in pancreatic ductal adenocarcinoma

Kelly E Craven; Jesse Gore; Murray Korc

doi:10.1016/j.canlet.2015.11.047

Overview of pre-clinical and clinical studies targeting angiogenesis in pancreatic ductal adenocarcinoma

Cancer Lett. 2016 Oct 10;381(1):201-10. doi: 10.1016/j.canlet.2015.11.047. Epub 2015 Dec 23.

Authors

Kelly E Craven¹, Jesse Gore², Murray Korc³

Affiliations

¹ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
² Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Pancreatic Cancer Signature Center, Indiana University Simon Cancer Center, Indianapolis, IN 46202, USA.
³ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Pancreatic Cancer Signature Center, Indiana University Simon Cancer Center, Indianapolis, IN 46202, USA. Electronic address: mkorc@iu.edu.

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.

Keywords: Angiogenesis; Pancreatic cancer; Vascular endothelial growth factor (VEGF).

Publication types

Review
Research Support, N.I.H., Extramural

MeSH terms

Angiogenesis Inhibitors / adverse effects
Angiogenesis Inhibitors / therapeutic use*
Angiogenic Proteins / antagonists & inhibitors*
Angiogenic Proteins / metabolism
Animals
Carcinoma, Pancreatic Ductal / blood supply
Carcinoma, Pancreatic Ductal / drug therapy*
Carcinoma, Pancreatic Ductal / metabolism
Carcinoma, Pancreatic Ductal / pathology
Drug Resistance, Neoplasm
Humans
Molecular Targeted Therapy
Neovascularization, Pathologic*
Pancreatic Neoplasms / blood supply
Pancreatic Neoplasms / drug therapy*
Pancreatic Neoplasms / metabolism
Pancreatic Neoplasms / pathology
Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
Receptors, Vascular Endothelial Growth Factor / metabolism
Signal Transduction / drug effects
Tumor Microenvironment
Vascular Endothelial Growth Factor A / antagonists & inhibitors
Vascular Endothelial Growth Factor A / metabolism

Substances

Angiogenesis Inhibitors
Angiogenic Proteins
Vascular Endothelial Growth Factor A
Receptors, Vascular Endothelial Growth Factor

Abstract

Publication types

MeSH terms

Substances

Grants and funding