Published online Mar 7, 2014. doi: 10.3748/wjg.v20.i9.2218
Revised: January 2, 2014
Accepted: January 19, 2014
Published online: March 7, 2014
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.
Core tip: Opioid growth factor (OGF) biotherapy for human pancreatic cancer is based on inhibition of DNA synthesis by upregulation of cyclin-dependent inhibitory kinases. Preclinical studies using human pancreatic cancer cell lines have demonstrated that OGF interaction with its selective receptor OGF receptor (OGFr) is a physiological determinant of cell proliferation. Addition of OGF to standard chemotherapies enhances the efficacy of treatment. Studies in nude mice confirm that the OGF-OGFr axis regulates pancreatic cancer progression. Clinical trials using OGF for treatment of patients with unresectable pancreatic tumors reveal that OGF is a novel endogenous opioid that is safe, non-toxic, elicits negligible side effects and reduces pancreatic tumor size in persons who have failed other therapies.