Targeting the opioid growth factor: opioid growth factor receptor axis for treatment of human ovarian cancer

Exp Biol Med (Maywood). 2013 May;238(5):579-87. doi: 10.1177/1535370213488483.


The opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis is a biological pathway that is present in human ovarian cancer cells and tissues. OGF, chemically termed [Met(5)]-enkephalin, is an endogenous opioid peptide that interfaces with OGFr to delay cells moving through the cell cycle by upregulation of cyclin-dependent inhibitory kinase pathways. OGF inhibitory activity is dose dependent, receptor mediated, reversible, protein and RNA dependent, but not related to apoptosis or necrosis. The OGF-OGFr axis can be targeted for treatment of human ovarian cancer by (i) administration of exogenous OGF, (ii) genetic manipulation to over-express OGFr and (iii) use of low dosages of naltrexone, an opioid antagonist, which stimulates production of OGF and OGFr for subsequent interaction following blockade of the receptor. The OGF-OGFr axis may be a feasible target for treatment of cancer of the ovary (i) in a prophylactic fashion, (ii) following cytoreduction or (iii) in conjunction with standard chemotherapy for additive effectiveness. In summary, preclinical data support the transition of these novel therapies for treatment of human ovarian cancer from the bench to bedside to provide additional targets for treatment of this devastating disease.

Keywords: DNA synthesis; OGF; OGFr; [Met5]-enkephalin; cell proliferation; naltrexone; ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Naltrexone / therapeutic use*
  • Narcotic Antagonists / therapeutic use*
  • Necrosis
  • Neoplasm Proteins* / antagonists & inhibitors
  • Neoplasm Proteins* / metabolism
  • Opioid Peptides / metabolism
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Receptors, Opioid* / metabolism
  • Up-Regulation / drug effects


  • Narcotic Antagonists
  • Neoplasm Proteins
  • Opioid Peptides
  • Receptors, Opioid
  • methionine-enkephalin receptor
  • Naltrexone