Abstract 4642: Combined glycolytic inhibition and anti-vascular treatment in retinoblastoma: Novel strategy for tumor control avoids chemotherapy

Abstract

Abstract Purpose: The purpose of this study was to evaluate the combination treatment of glycolytic inhibitors and anti-angiogenic agents on tumor burden and hypoxia in advanced retinoblastoma using the LHbetaTag murine transgenic retinoblastoma model. Methods: Under IACUC protocol, thirty advanced LHbetaTag mice (16 weeks of age) were divided into 5 groups (n=6 per group) and treated with periocular injections of (a) saline, (b) 2-deoxy-glucose (2-DG), (c) anecortave acetate (AA) or (d) 2-DG plus AA (one day post AA treatment) or (e) 2-DG plus AA (one week post AA treatment). Eyes were enucleated at 21 weeks and tumor sections were analyzed for tumor burden and intra-tumoral hypoxia. Results: Combined treatment with 2-DG and AA (both 2-DG one day and one week post AA treatment) showed significant reduction in tumor burden compared to saline control (61% and 56% respectively, p <.001). Eyes treated with 2-DG one day post AA injection showed a significant tumor burden reduction as compared to 2-DG alone or 2-DG plus AA injected after one week (p<01). Further, intra-tumoral hypoxia was eliminated in 2-DG treated eyes at one day post AA injection and was significantly reduced in 2-DG eyes treated one week after AA injection (p<.0001). Conclusion: Combination focal therapy with glycolytic inhibitors and angiogenic inhibitors significantly enhanced tumor control and reduced tumor hypoxia. Treatment timing greatly impacted the effect of combined treatment. Combination therapy with 2-DG and AA was as effective as current chemotherapy regimens in the treatment of LHbetaTag murine transgenic retinoblastoma and may potentially serve as an alternative treatment strategy for advanced pediatric retinoblastoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4642. doi:1538-7445.AM2012-4642