UniPR1331, a small molecule targeting Eph/ephrin interaction, prolongs survival in glioblastoma and potentiates the effect of antiangiogenic therapy in mice

Oncotarget
Claudio FestucciaMassimiliano Tognolini

Abstract

Glioblastoma multiforme (GBM) is the most malignant brain tumor, showing high resistance to standard therapeutic approaches that combine surgery, radiotherapy, and chemotherapy. As opposed to healthy tissues, EphA2 has been found highly expressed in specimens of glioblastoma, and increased expression of EphA2 has been shown to correlate with poor survival rates. Accordingly, agents blocking Eph receptor activity could represent a new therapeutic approach. Herein, we demonstrate that UniPR1331, a pan Eph receptor antagonist, possesses significant in vivo anti-angiogenic and anti-vasculogenic properties which lead to a significant anti-tumor activity in xenograft and orthotopic models of GBM. UniPR1331 halved the final volume of tumors when tested in xenografts (p<0.01) and enhanced the disease-free survival of treated animals in the orthotopic models of GBM both by using U87MG cells (40 vs 24 days of control, p<0.05) or TPC8 cells (52 vs 16 days, p<0.01). Further, the association of UniPR1331 with the anti-VEGF antibody Bevacizumab significantly increased the efficacy of both monotherapies in all tested models. Overall, our data promote UniPR1331 as a novel tool for tackling GBM.

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Citations

Jan 19, 2019·Cancer Science·Katsuaki Ieguchi, Yoshiro Maru
Mar 22, 2020·Expert Opinion on Therapeutic Targets·Carmine GiorgioMassimiliano Tognolini
Apr 23, 2020·Pharmaceuticals·Miriam CorradoMassimiliano Tognolini
Aug 20, 2020·Journal of Hematology & Oncology·Ta XiaoMin Su
May 14, 2020·Pharmaceuticals·Ahmed F SalemMaurizio Pellecchia
Oct 22, 2018·The International Journal of Biochemistry & Cell Biology·Nayanendu SahaDimitar B Nikolov
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Parima UdompholkulMaurizio Pellecchia

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Methods Mentioned

BETA
xenograft
xenografts
FACS
PCR

Clinical Trials Mentioned

NCT02004717
NCT02252211
NCT02078752

Software Mentioned

PicTar2
miRanda
miRmap
microTv4
miRNAMap
doRiNA
MiRWalk
Cytoscape
Targetscan6
CDS

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