Novel therapies in GBM. RTKs and survival signaling pathways are major drug targets in GBM. Receptors have been targeted extracellularly by monoclonal antibodies or intracellularly at the tyrosine kinase domain. Major nodes in survival signaling pathways (P13K, AKT, mTOR) have been the focus of intense study and drug development. More recent approaches include stem-cell targeting (GSIs), inhibition of DNA rapair (PARP inhibitors), and targeting a host of cellular pathways through microRNA manipulation. Novel tumor cell killing approaches are also being studied. Oncolytic virus therapy, either alone or in combination with targeted agent delivery and immunotherapy, are being employed to efficiently kill tumor cells while sparing normal tissue. RTK, receptor tyrosine kinase; EGFR, epidermal growth factor receptor; VEGFR, vascular endothelial growth factor receptor; IGFR, insulin-like growth factor receptor 1; PDGFR, platelet-derived growth factor receptor; mTor, mammalian target of rapamycin; GSI, gamma-secretase inhibitor; APC, antigen-presenting cell; CTL, cytotoxic T lymphocyte, MHC class I, major histocompatibility complex I; PARP, poly(ADP-ribose) polymerase; HDAC, histone deacetylase inhibitor.
