Modulation of the OGF‐OGFr Axis Suppresses Progression of Head and Neck Cancer

Squamous cell carcinoma of the head and neck (SCCHN) constitutes 2% of deaths annually in the U.S., and treatment modalities are needed. The opioid growth factor (OGF)‐OGF receptor (OGFr) axis, a tonically active pathway in SCCHN, regulates cell proliferation by increasing p16 and p21 and inhibiting DNA synthesis. This study investigated whether modulation of the OGF‐OGFr system by i) exogenous OGF, ii) intermittent opioid receptor blockade with a low dose of naltrexone (LDN) or iii) upregulation of OGFr by imiquimod altered the course of established SCCHN tumors in nude mice. At the time of tumor appearance, animals received OGF (10 mg/kg, i.p.) or LDN (0.1 mg/kg NTX i.p.) 1x, 3x, or 7x/wk, imiquimod cream (Aldara) topically 1x or 3x/wk, or saline. Relative to control neoplasias, tumor volumes on the day of termination of mice receiving OGF 1x, 3x, or 7x/wk were decreased 53%, 44%, and 64%, respectively, whereas LDN treated mice (1x, 3x, 7x/wk) had reductions of 33%, 53%, and 75%, respectively. Tumor volumes of mice treated with imiquimod 3x/wk directly on the tumor or even in a distant location, but not 1x/wk, had tumor volumes that were reduced 65% and 50%, respectively, from controls. DNA synthesis rates in tumors of OGF, LDN, or imiquimod treated were reduced from controls. These data suggest that alteration of the OGF‐OGFr system represents novel therapeutic approaches for treatment of SCCHN cancer.