EphB4/EphrinB2 therapeutics in Rhabdomyosarcoma

Matthew E. Randolph, Megan M. Cleary, Zia Bajwa, Matthew N. Svalina, Michael C. Young, Atiya Mansoor, Pali Kaur, Carol J. Bult, Martin W. Goros, Joel E. Michalek, Sunny Xiang, James Keck, Valery Krasnoperov, Parkash Gill, Charles Keller

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbere0183161
JournalPloS one
Volume12
Issue number8
DOIs
StatePublished - Aug 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Randolph, M. E., Cleary, M. M., Bajwa, Z., Svalina, M. N., Young, M. C., Mansoor, A., Kaur, P., Bult, C. J., Goros, M. W., Michalek, J. E., Xiang, S., Keck, J., Krasnoperov, V., Gill, P., & Keller, C. (2017). EphB4/EphrinB2 therapeutics in Rhabdomyosarcoma. PloS one, 12(8), [e0183161]. https://doi.org/10.1371/journal.pone.0183161