Abstract 2050: 2-Deoxy-D-Glucose (2-DG) as a glycolytic inhibitor in the treatment of retinoblastoma

Abstract

Abstract Purpose: The aim of the current study is to assess the impact of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on tumor burden and hypoxia in the LHBETATAG retinal tumors. Methods: Group A: 17-week-old LHBETATAG transgenic mice (n=30) received periocular injections of saline and 2-DG (62.5, 125, 250, and 500mg/kg). Injections were given 2 times a week for 3 weeks. Group B: 4-week-old mice received oral delivery of 2-DG in custom made food pellets and were treated for either 8 or 18 weeks. 17-week-old mice received oral 2-DG for 8 weeks. At the time of enucleation, all eye samples were snap frozen and analyzed for tumor burden and hypoxic regions using immunohistochemistry. Results: Following injections of 2-DG, tumor control was not different between the control and the lowest two doses (62.5 and 125mg/kg). However, the difference in tumor burden was significant from 250mg/kg dose (p<0.015) and 500mg/kg dose (p<0.001) with 9.7 and 23% tumor burden decrease, respectively. At all doses of periocular 2-DG, the percent hypoxia following drug treatment were lower relative to controls (p<0.001), with a hypoxia decrease in the lowest dose to 2.4% compared to 21% in controls. Following oral delivery of 2-DG, there was a difference between the groups treated with 2-DG and the control groups (p<0.010). A 20% reduction in tumor burden was found in the 8 weeks early treated, a 50% reduction in the 18 weeks early treated, and a 35% reduction in the 8 weeks late treated group. The percent hypoxia was lower relative to controls in the 8 weeks and 18 weeks early treated groups (p<0.001) with a 40% and 50% reduction, respectively. The percent hypoxia did not change following treatment in the treated late group. Conclusions: This study exhibits the efficacy of focal 2-DG as potential therapy to decrease both intratumoral hypoxia and tumor burden. The current study also shows that the non-invasive oral delivery 2-DG treatment has similar or better effects on the tumor depending on the treatment schedule used. In advanced disease of LHBETATAG retinal tumors, hypoxia is increasingly present. The use of glycolytic inhibitors as a therapeutic strategy has the potential to enhance current retinoblastoma treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2050. doi:10.1158/1538-7445.AM2011-2050