Abstract 2682: ELTD1 as a target for anti-cancer therapy in rodent gliomas

Abstract

Abstract Despite current therapies, glioblastoma multiforme (GBM) is a devastating cancer with a very poor prognosis. Specific protein biomarkers for GBM enable not only new prognostic avenues to tailor treatment, but valuable therapeutic targets to interfere with GBM growth. We recently discovered a new biomarker for high-grade gliomas, ELTD1 (epidermal growth factor, latrophilin, and 7 transmembrane domain-containing protein 1 on chromosome 1), via a novel bioinformatics approach, GAMMA (Global microarray meta-analysis). ELTD1 was found to be significantly higher (p<0.05) in high-grade gliomas (50 patients) compared with low-grade gliomas (21 patients). ELTD1 gene expression was found to be associated with tumor grade, survival across grade, and an increase in the mesenchymal subtype. From our previous results we hypothesized that ELTD1 may be a potential therapeutic target in high-grade gliomas. We tested the hypothesis in an orthotopic GL261 mouse glioma model in animals treated with an anrti-ELTD1 antibody, compared to those that were treated with an anti-VEGF antibody or an anti-c-Met antibody, and untreated tumors. Tumor volumes were measured by morphological magnetic resonance imaging (MRI). Our data in orthotopic GL261 glioma-bearing mice shows that injection of anti-ELTD1 antibodies lead to a significant decrease in tumor volumes (p<0.0001) and a significant increase in animal survival (p<0.05), superior to that achieved by a mouse anti-VEGF antibody or an antibody against c-Met, when compared to untreated mice. Tumor volumes were obtained at various time-points, and compared at 21 days following intracerebral implantation of GL261 cells in male C57BL6 mice. These tumor volumes at 21 days were 86.03+/-41.54 mm3 for untreated mice (n=5); 13.04+/-5.35 mm3 for anti-ELTD1 treated mice (n=5); 33.16+/-12.48 mm3 for anti-VEGF treated mice (n=4); and 28.49+/-11.11 mm3 for anti-c-Met treated mice (n=5). The mean days of survival for untreated, ELTD1, VEGF or c-Met treatment groups were 23.8+/-1.79, 28.2+/-2.39, 27+/-1.15 or 27+/-1.87 days, respectively. These pre-clinical results indicate that an additional therapy in the form of an anti-ELTD1 antibody either as a sole agent or in combination with current or new therapies could potentially provide high-grade glioma patients with a better prognostic outcome. Citation Format: Rheal A. Towner, Richard Pody, Nataliya Smith, Debra Saunders, Charity Njoku, Jonathan D. Wren. ELTD1 as a target for anti-cancer therapy in rodent gliomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2682. doi:10.1158/1538-7445.AM2014-2682