Enrico Martin

171 Emerging therapeutic targets mTOR CXCR Angiogenesis ER ER Oncolytic Viruses STAT3 PI3K PDK1 Akt Neurofibromin PTEN Growth Factors VEGFR VEGFR RAF ERK MEK TAZ/YAP Cyclin D1 CDK4/6 RAS Epigenetic modulation AURKA RTKs EGFR C-KIT PDGFR JAK JAK PD1 PDL1 T-cell CTLA4 PAK1 BET HDAC MET Figure 2 Cellular pathways in MPNST. AURKA: aurora kinase A; BET: bromo- and extra-terminal domain; CDK: cyclin-dependent kinase; CTLA4: cytotoxic T-lymphocyte associated protein 4; CXCR: CXC-chemokine receptor; EGFR: epidermal growth factor receptor; ER: estrogen receptor; ERK: extracellular signal-regulated kinases; HDAC: histone deacetylase; JAK: Janus kinase; MEK: mi- togen-activated protein kinase kinase; mTOR: mammalian target of rapamycin; PD1: programmed cell death protein 1; PDGFR: platelet-derived growth factor receptor; PDK1: phosphoinositide-de- pendent kinase-1; PDL1: programmed death-ligand 1; PI3K: phosphoinositide 3-kinase; PTEN: phosphatase and tensin homolog; STAT3: signal transducer and activator of transcription 3; VEGFR: vascular endothelial growth factor receptor Immunotherapy and oncolytic viruses – in vivo Next to tumor cell specific targeting, immunotherapy may also play a role in MPNST treatment. With an evolving role in other cancer types, no in vivo studies have thus far been published investigating immunotherapy regimens specifically in MPNST. Oncolytic viruses are thought to affect tumors in several ways, one of which involves the upregulation of the immune system. Eight studies investigated the effect of oncolytic viruses in MPNST in vivo ( Table 1 ). Seven studies used an oncolytic herpes simplex virus (oHSV) with mostly intermediate to high effect (10/12 cell lines) on tumor growth. 68–74 One study used an oncolytic measles virus (oMV) and showed high efficacy in one xenograft model, but low effect in another. 75 Almost all studies looked at survival and showed a statistically significant benefit for treatment with oncolytic viruses 7