PDGFRβ reverses EphB4 signaling in alveolar rhabdomyosarcoma
Many congratulations to Imran (Aslam) for his publication, PDGFRβ reverses EphB4 signaling in alveolar rhabdomyosarcoma, today in the Proceedings of the National Academy of Sciences of the USA. This study was a collaboration of the Tyner, Druker and Keller laboratories - highlighting some key growth factor receptor targets in this disease. This study was funded in part by the Howard Hughes Medical Institute, the National Cancer Institute, and the Joanna McAfee Childhood Cancer Foundation. [from Keller Lab Blog]
The significance of this work, as described in the paper:
Effective targeted therapies to complement already intensive chemotherapy are much needed for the childhood muscle cancer rhabdomyosarcoma, yet few targeted agents have been identified that improve long-term survival. In particular, the alveolar subtype of rhabdomyosarcoma accounts for disproportionate
mortality. Herein, the receptor tyrosine kinase EphB4 is identified as a potential two-way switch for alveolar rhabdomyosarcoma. Whereas the typical EphB4 ligand, EphrinB2, drives tumor cells toward apoptosis, the interaction between EphB4 and another receptor tyrosine kinase, PDGFRβ, drives tumors to
proliferate in the presence of the PDGFRβ ligand, PDGF-BB. The Food and Drug Administration-approved dual EphB4-PDGFRβ inhibitor, dasatinib, is found to have significant preclinical activity, which is clinically relevant because EphB4 and PDGFRβ are independent poor prognostic factors in this childhood disease.