Opioid Growth Factor and the Treatment of Human Pancreatic Cancer: A Review

World J Gastroenterol. 2014 Mar 7;20(9):2218-23. doi: 10.3748/wjg.v20.i9.2218.

Abstract

Opioid growth factor (OGF), chemically termed [Met⁵]-enkephalin, and its receptor, OGF receptor (OGFr), form a biological axis that tonically regulates cell proliferation by delaying the G₁/S interface of the cell cycle under homeostatic conditions or in neoplasia. Modulation of the OGF-OGFr pathway mediates the course of pancreatic cancer, with exogenous OGF or upregulation of OGFr repressing growth of human pancreatic cancer cells in culture and in nude mice. OGF therapy alone or in combination with standard chemotherapies such as gemcitabine and 5-fluorouracil results in enhanced inhibition of DNA synthesis and tumor growth. Molecular manipulation of OGFr confirms that the receptor is specific for OGF's inhibitory action. Preclinical studies have warranted Phase I and Phase II clinical trials using OGF infusions as a treatment for patients with advanced, unresectable pancreatic cancers. OGF, an endogenous neuropeptide, is a safe, non-toxic, and effective biotherapy that utilizes the OGF-OGFr axis to mediate pancreatic tumor progression.

Keywords: DNA synthesis; Enkephalins; Nude mice; Opioids; Pancreatic adenocarcinoma; Receptor transfection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Enkephalin, Methionine / metabolism
  • Enkephalin, Methionine / therapeutic use*
  • Humans
  • Mice
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Receptors, Opioid / agonists
  • Receptors, Opioid / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Tumor Burden / drug effects

Substances

  • Antineoplastic Agents
  • Receptors, Opioid
  • methionine-enkephalin receptor
  • Enkephalin, Methionine