EphB4/EphrinB2 therapeutics in Rhabdomyosarcoma.
Document Type
Article
Publication Date
2017
JAX Source
PLoS One 2017 Aug 17; 12(8):e0183161.
Volume
12
Issue
8
First Page
0183161
Last Page
0183161
ISSN
1932-6203
PMID
28817624
DOI
https://doi.org/10.1371/journal.pone.0183161
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. PLoS One 2017 Aug 17; 12(8):e0183161.
Recommended Citation
Randolph M,
Cleary M,
Bajwa Z,
Svalina M,
Young M,
Mansoor A,
Kaur P,
Bult C,
Goros M,
Michalek J,
Xiang S,
Keck JG,
Krasnoperov V,
Gill P,
Keller C.
EphB4/EphrinB2 therapeutics in Rhabdomyosarcoma. PLoS One 2017 Aug 17; 12(8):e0183161.