Oncotarget

Research Papers:

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

Claudio Festuccia, Giovanni Luca Gravina, Carmine Giorgio, Andrea Mancini, Cristina Pellegrini, Alessandro Colapietro, Simona Delle Monache, Maria Giovanna Maturo, Roberta Sferra, Paola Chiodelli, Marco Rusnati, Annamaria Cantoni, Riccardo Castelli, Federica Vacondio, Alessio Lodola and Massimiliano Tognolini _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2018; 9:24347-24363. https://doi.org/10.18632/oncotarget.25272

Metrics: PDF 1180 views  |   HTML 1847 views  |   ?  


Abstract

Claudio Festuccia1,*, Giovanni Luca Gravina1,*, Carmine Giorgio2, Andrea Mancini1, Cristina Pellegrini1, Alessandro Colapietro1, Simona Delle Monache1, Maria Giovanna Maturo1, Roberta Sferra1, Paola Chiodelli3, Marco Rusnati3, Annamaria Cantoni4, Riccardo Castelli2, Federica Vacondio2, Alessio Lodola2 and Massimiliano Tognolini2

1Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, 67100, L'Aquila, Italy

2Department of Food and Drug, University of Parma, 43124, Parma, Italy

3Department of Molecular and Translational Medicine, University of Brescia, 25123, Brescia, Italy

4Department of Veterinary Sciences, University of Parma, 43100, Parma, Italy

*These authors have contributed equally to this work

Correspondence to:

Massimiliano Tognolini, email: massimiliano.tognolini@unipr.it

Alessio Lodola, email: alessio.lodola@unipr.it

Claudio Festuccia, email: claudio.festuccia@univaq.it

Keywords: glioblastoma; Eph/ephrin; angiogenesis; PPI-i; UniPR1331

Received: September 12, 2017     Accepted: April 07, 2018     Published: May 11, 2018

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 25272