The role of hypoxia in pancreatic cancer: a potential therapeutic target?

Expert Rev Gastroenterol Hepatol. 2016;10(3):301-16. doi: 10.1586/17474124.2016.1117386. Epub 2015 Nov 27.

Abstract

One of the key factors that correlates with poor survival of patients with pancreatic cancer is the extent of hypoxic areas within the tumor tissue. The adaptation of pancreatic cancer cells to limited oxygen delivery promotes the induction of an invasive and treatment-resistant phenotype, triggering metastases at an early stage of tumor development, which resist in most cases adjuvant therapies following tumor resection. In this article, the authors summarize the evidence demonstrating the significance of hypoxia in pancreatic cancer pathogenesis and discuss the possible hypoxia-induced mechanisms underlying its aggressive nature. We then conclude with promising strategies that target hypoxia-adapted pancreatic cancer cells.

Keywords: PEGPH20; Pancreatic cancer; TH-302; cancer stem cell; desmoplasia; epithelial-to-mesenchymal transition; hypoxia; metabolism.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cell Hypoxia
  • Drug Design
  • Humans
  • Hypoxia-Inducible Factor 1 / metabolism
  • Molecular Targeted Therapy
  • Oxygen / metabolism*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Phenotype
  • Signal Transduction
  • Tumor Microenvironment*

Substances

  • Antineoplastic Agents
  • Hypoxia-Inducible Factor 1
  • Oxygen