Simultaneous targeting of Eph receptors in glioblastoma

摘要: // Sara Ferluga 1 , Carla Maria Lema Tome 2 Denise Mazess Herpai Ralph D’Agostino 3 Waldemar Debinski Department of Cancer Biology, Radiation Oncology and Neurosurgery, Brain Tumor Center Excellence, Comprehensive Wake Forest Baptist Medical Center, School Medicine, Boulevard, Winston-Salem, NC 27157, USA Neurobiology Anatomy, Biostatistical Sciences, Section on Biostatistics, University Health NC, Correspondence to: Debinski, email: debinski@wakehealth.edu Keywords: Eph receptors, ephrin-A5, glioblastoma, cytotoxin, molecular targeting Received: October 12, 2015      Accepted: July 16, 2016      Published: August 1, 2016 ABSTRACT tyrosine kinase receptors are frequently overexpressed functional in many cancers, they attractive candidates for targeted therapy. Here, we analyzed the expression receptor A3, one most up-regulated factors glioblastoma cells cultured under tumorsphere-forming conditions, together with EphA2 EphB2 receptors. EphA3 was up to 60% tumors tested, but not normal brain. localized scattered areas tumor, invasive ring, niches near tumor vessels. co-localized macrophage/leukocyte markers, suggesting tumor-infiltrating bone marrow origin. We took advantage fact that ephrinA5 (eA5) is a ligand binds EphA3, used it construct novel anti-glioblastoma cytotoxin. The eA5-based cytotoxin potently specifically killed an IC 50 at least 10 -11 M. This similar cytotoxins will simultaneously target different compartments while mitigating heterogeneity.