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Efficacy and selectivity of nilotinib on NF1-associated tumors in vitro

Jiang, W and Schnabel, C and Spyra, M and Mautner, VF and Friedrich, RE and Hagel, C and Manley, PW and Kluwe, L (2014) Efficacy and selectivity of nilotinib on NF1-associated tumors in vitro. JOURNAL OF NEURO-ONCOLOGY. pp. 231-236.

Abstract

Neurofibromatosis type 1 is a tumor suppressor gene disorder which predisposes patients to cutaneous neurofibromas, plexiform neurofibromas (PNFs) and malignant peripheral nerve sheath tumors (MPNSTs) among other neoplasias and manifestation. In this study, we examined the efficiency of nilotinib on PNF-derived Schwann cells and on cells of established MPNST lines in vitro. Nilotinib treatment for 10 days led to decreased proliferation, viability and vitality of the cells with 50 % inhibitory concentration (IC50) for proliferation varying from 3.1 to 9.0 mu M. We further addressed selectivity of the drug for tumor cells by simultaneously examining its efficacy on tumor cells (Schwann cells) and non-tumor cells (fibroblasts) from the same tumor. For four out of the six PNFs studied, IC50 was lower in Schwann cells than in fibroblasts for all parameters measured (proliferation, vitality and viability), indicating good drug selectivity. In addition, nilotinib induced apoptosis and suppressed collagenase activity. Our results suggest that nilotinib may provide a treatment option for some PNFs and MPNSTs and our in vitro model of comparative treatment on tumor and non-tumor cells may provide a prototype of preclinical drug screening system toward personalized treatment

Item Type: Article
Additional Information: NIBR author: Manley, P institute: NIBR- address only contributor address: Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Lab Tumor Genet, D-20246 Hamburg, Germany ; Univ Med Ctr Hamburg Eppendorf, Dept Maxillofacial Surg, D-20246 Hamburg, Germany ; Univ Med Ctr Hamburg Eppendorf, Inst Neuropathol, D-20246 Hamburg, Germany ; Novartis Inst Biomed Res, Basel, Switzerland ; Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Lab Tumor Genet, D-20246 Hamburg, Germany, Univ Med Ctr Hamburg Eppendorf, Dept Maxillofacial Surg, D-20246 Hamburg, Germany kluwe@uke.de; Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Lab Tumor Genet, D-20246 Hamburg, Germany; Kluwe, L; Univ Med Ctr Hamburg Eppendorf, Dept Neurol, Lab Tumor Genet, Bldg O48,4th Floor,Martinistr 52, D-20246 Hamburg, Germany
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/22659

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