Enrico Martin

169 Emerging therapeutic targets CDK4/6 and EZH2 act via influence on the cell cycle; in vivo studies showed that their inhibition has intermediate effect on tumor growth. 64,65 XPO1 is the main nuclear export protein and transports proteins such as survivin. One in vivo study found intermediate effect of XPO1 inhibition combined with proteasome inhibitor carfilzomib. 66 Table 2 Published clinical trials. Author, year Study Design N Age Drug Pathway Outcome RR PFS OS Membrane targets Albritton, 2006 Phase II unresectable or metastatic MPNST 20 ≥18 Erlotinib EGFR 1 SD, 19 PD 2 months 4 months Chugh, 2009 Phase II metastatic or recurrent sarcomas 5 ≥10 Imatinib Multikinase (incl. c-Kit) 1 SD, 4 PD NA NA Maki, 2009 Phase II metastatic or recurrent sarcomas 12 ≥18 Sorafenib Multikinase (incl. VEGFR) 3 SD, 9 PD 1.7 months 4.9 months Schuetze, 2016 Phase II high-grade, advanced sarcomas 14 ≥13 Dasatinib Multikinase (incl. BCR/ ABL) 14 PD 2-month: 14% 4-month: 7% NA Cytoplasmic targets Widemann, 2016 Phase II recurrent or metastatic MPNST 25 ≥18 Everolimus + Bevacizumab mTOR, VEGF 3 SD, 22 PD NA NA Nuclear targets Dickson, 2016 Phase II advanced or metastatic sarcomas 10 ≥18 Alisertib AURKA No response (SD and PD) 13 weeks, 12-week: 60% 69 weeks AURKA: aurora kinase A, CI: confidence interval, CR: complete remission, EGFR: endothelial growth factor receptor, mTOR: mammalian target of rapamycin, N: total MPNST patients included, NA: not available, OS: overall survival, PD: progressive disease, PFS: progression free survival, RR: response rate, SD: stable disease, VEGF: vascular endothelial growth factor, VEGFR: vascular endothelial growth factor 7