EphB4/EphrinB2 therapeutics in Rhabdomyosarcoma.
PLoS One 2017 Aug 17; 12(8):e0183161.
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.
Randolph, Matthew E; Cleary, Megan M; Bajwa, Zia; Svalina, Matthew N; Young, Michael C; Mansoor, Atiya; Kaur, Pali; Bult, Carol J; Goros, Martin W; Michalek, Joel E; Xiang, Sunny; Keck, James G.; Krasnoperov, Valery; Gill, Parkash; and Keller, Charles, "EphB4/EphrinB2 therapeutics in Rhabdomyosarcoma." (2017). Faculty Research 2017. 164.