Inhibition of PDGFR May Be a Viable Treatment Option for Meningiomas
Meningiomas are the most common primary central nervous system tumor. Surgery is the principal mode of treatment for meningiomas and there is no agreement on the benefit of adjuvant therapies. Our screening efforts have identified platelet-derived growth factor receptor (PDGFR) inhibitors as a prospective treatment for meningioma. Utilizing our screening platform, we were able to screen meningiomas against a tyrosine kinase receptor (TKR) drug library and identify compounds that significantly reduced cell viability. Of the compounds examined, our screen identified PDGFR and vascular endothelial growth factor receptor (VEGFR) inhibitors to be some of the most effective. Given that VEGFR inhibition is already accessible in the clinic, we chose to focus our efforts on PDGFR. In order to fully elucidate PDGFR-family inhibitors, we conducted individual dose curve screening assays with compounds that selectively target the isoforms of PDGFR. In this study, we present ponatinib, a PDGFR-alpha and VEGFR inhibitor, as the most effective PDGFR-targeted compound, implicating its role in potential meningioma treatment.
