TY - JOUR
T1 - Targeting the opioid growth factor
T2 - Opioid growth factor receptor axis for treatment of human ovarian cancer
AU - Zagon, Ian S.
AU - Donahue, Renee
AU - Mclaughlin, Patricia J.
N1 - Funding Information:
These research investigations were supported in part by funding from the Paul K and Anna E Shockey Family Foundation, Bonnie and Ken Shockey family, and the Zagon/Kostel families. There are no conflicts of interest. Penn State University holds patents (ISZ and PJM co-inventors) on the use of OGF for treatment of pancreatic and gastrointestinal cancer, and has recently licensed them to TNI Biotech.
PY - 2013/8
Y1 - 2013/8
N2 - 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 [Met5]-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 OGFOGFr 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.
AB - 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 [Met5]-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 OGFOGFr 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.
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U2 - 10.1177/1535370213488483
DO - 10.1177/1535370213488483
M3 - Article
C2 - 23856908
AN - SCOPUS:84881605592
SN - 1535-3702
VL - 238
SP - 579
EP - 587
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 5
ER -
