Mitochondrial uncoupling protein 2 and pancreatic cancer: a new potential target therapy

World J Gastroenterol. 2015 Mar 21;21(11):3232-8. doi: 10.3748/wjg.v21.i11.3232.

Abstract

Overall 5-years survival of pancreatic cancer patients is nearly 5%, making this cancer type one of the most lethal neoplasia. Furthermore, the incidence rate of pancreatic cancer has a growing trend that determines a constant increase in the number of deceases caused by this pathology. The poor prognosis of pancreatic cancer is mainly caused by delayed diagnosis, early metastasis of tumor, and resistance to almost all tested cytotoxic drugs. In this respect, the identification of novel potential targets for new and efficient therapies should be strongly encouraged in order to improve the clinical management of pancreatic cancer. Some studies have shown that the mitochondrial uncoupling protein 2 (UCP2) is over-expressed in pancreatic cancer as compared to adjacent normal tissues. In addition, recent discoveries established a key role of UCP2 in protecting cancer cells from an excessive production of mitochondrial superoxide ions and in the promotion of cancer cell metabolic reprogramming, including aerobic glycolysis stimulation, promotion of cancer progression. These observations together with the demonstration that UCP2 repression can synergize with standard chemotherapy to inhibit pancreatic cancer cell growth provide the molecular rationale to consider UCP2 as a potential therapeutic target for pancreatic cancer. In this editorial, recent advances describing the relationship between cancer development and mitochondrial UCP2 activity are critically provided.

Keywords: Metabolism; Pancreatic cancer; Reactive oxygen species; Target therapy; Uncoupling protein 2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / metabolism*
  • Humans
  • Ion Channels / antagonists & inhibitors
  • Ion Channels / metabolism*
  • Mitochondrial Proteins / antagonists & inhibitors
  • Mitochondrial Proteins / metabolism*
  • Molecular Targeted Therapy
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Signal Transduction* / drug effects
  • Uncoupling Protein 2
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Ion Channels
  • Mitochondrial Proteins
  • UCP2 protein, human
  • Uncoupling Protein 2