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PLoS One. 2017 Aug 17;12(8):e0183161. doi: 10.1371/journal.pone.0183161. eCollection 2017.

EphB4/EphrinB2 therapeutics in Rhabdomyosarcoma.

Author information

1
Children's Cancer Therapy Development Institute, Beaverton, Oregon, United States of America.
2
Department of Pediatrics, Oregon Health & Science University, Portland, Oregon, United States of America.
3
Department of Pathology, Oregon Health & Science University, Portland, Oregon, United States of America.
4
The Jackson Laboratory Cancer Center, The Jackson Laboratory, Bar Harbor, Maine, United States of America.
5
Department of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio, Texas, United States of America.
6
Vasgene Therapeutics, Los Angeles, California, United States of America.

Abstract

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma affecting children and is often diagnosed with concurrent metastases. Unfortunately, few effective therapies have been discovered that improve the long-term survival rate for children with metastatic disease. Here we determined effectiveness of targeting the receptor tyrosine kinase, EphB4, in both alveolar and embryonal RMS either directly through the inhibitory antibody, VasG3, or indirectly by blocking both forward and reverse signaling of EphB4 binding to EphrinB2, cognate ligand of EphB4. Clinically, EphB4 expression in eRMS was correlated with longer survival. Experimentally, inhibition of EphB4 with VasG3 in both aRMS and eRMS orthotopic xenograft and allograft models failed to alter tumor progression. Inhibition of EphB4 forward signaling using soluble EphB4 protein fused with murine serum albumin failed to affect eRMS model tumor progression, but did moderately slow progression in murine aRMS. We conclude that inhibition of EphB4 signaling with these agents is not a viable monotherapy for rhabdomyosarcoma.

PMID:
28817624
PMCID:
PMC5560593
DOI:
10.1371/journal.pone.0183161
[Indexed for MEDLINE]
Free PMC Article

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