Angiogenesis in pancreatic ductal adenocarcinoma: A controversial issue

Oncotarget. 2016 Sep 6;7(36):58649-58658. doi: 10.18632/oncotarget.10765.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) occurs in the majority of cases with early loco-regional spread and distant metastases at diagnosis, leading to dismal prognosis with a 5-year overall survival rate moderately over than 5%. This malignancy is largely resistant to chemotherapy and radiation, but the reasons of the refractoriness to the therapies is still unknown. Evidence is accumulating to indicate that the PDAC microenvironment and vascularity strongly contribute to the clinical features of this disease. In particular, PDAC is characterized by excessive dense extracellular matrix deposition associated to vasculature collapse and hypoxia with low drug delivery, explaining at least partly the low efficacy of antiangiogenic drugs in this cancer. Strategies aimed to modulate tumor stroma favoring vasculature perfusion and chemotherapeutics delivery are under investigation.

Keywords: angiogenesis; desmoplastic reaction; hypoxia; pancreatic ductal adenocarcinoma.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage*
  • Animals
  • Carcinoma, Pancreatic Ductal / diagnosis
  • Carcinoma, Pancreatic Ductal / pathology*
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Drug Delivery Systems
  • Extracellular Matrix / metabolism
  • Humans
  • Hypoxia
  • Inflammation
  • Mice
  • Neovascularization, Pathologic*
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / pathology*
  • Perfusion
  • Prognosis
  • Tumor Microenvironment

Substances

  • Angiogenesis Inhibitors