DRD2 and glioma: In addition, DRD2 activation is responsible for the mitogenic signaling in GBM through the sequential activation of RAP1-GTP, Raf-1 release, and MEK/ERK signaling [156].A selective inhibitor of DRD2 (ONC201), now in clinical trial for different solid tumors and recurrent GBM (NCT02525692) [157], inhibits the cellular proliferation of cancer stem cell-enriched neurospheres obtained from primary and recurrent GBM, and induces apoptosis in stem cell-like glioma cells [158,159].