Gemcitabine: metabolism and molecular mechanisms of action, sensitivity and chemoresistance in pancreatic cancer

Eur J Pharmacol. 2014 Oct 15;741:8-16. doi: 10.1016/j.ejphar.2014.07.041. Epub 2014 Jul 30.

Abstract

Gemcitabine is the first-line treatment for pancreatic adenocarcinoma, but is increasingly used to treat breast, bladder, and non-small cell lung cancers. Despite such broad use, intrinsic and acquired chemoresistance is common. In general, the underlying mechanisms of chemoresistance are poorly understood. Here, current knowledge of gemcitabine metabolism, mechanisms of action, sensitivity and chemoresistance reported over the past two decades are reviewed; and we also offer new perspectives to improve gemcitabine efficacy with particular reference to the treatment of pancreatic cancer.

Keywords: Chemoresistance; Gemcitabine resistance; Molecular targets; NFκB; Pancreatic tumor.

Publication types

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

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / metabolism
  • Antimetabolites, Antineoplastic / pharmacology
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / metabolism
  • Deoxycytidine / pharmacology
  • Deoxycytidine / therapeutic use
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / physiology
  • Humans
  • Inflammation Mediators / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism

Substances

  • Antimetabolites, Antineoplastic
  • Inflammation Mediators
  • Deoxycytidine
  • gemcitabine