Suppression of proliferation of two independent NF1 malignant peripheral nerve sheath tumor cell lines by the pan-ErbB inhibitor CI-1033

Department of Pharmacology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Cancer biology & therapy (Impact Factor: 3.07). 01/2009; 7(12):1938-46. DOI: 10.4161/cbt.7.12.6942
Source: PubMed


Neurofibromatosis Type 1 (NF1) is characterized by the abnormal proliferation of neuroectodermal tissues and the development of certain tumors, particularly neurofibromas, which may progress into malignant peripheral nerve sheath tumors (MPNSTs). Effective pharmacological therapy for the treatment of NF1 tumors is currently unavailable and the prognosis for patients with MPNSTs is poor. Loss of neurofibromin correlates with increased expression of the epidermal growth factor receptor (EGFR) and ErbB2 tyrosine kinases and these kinases have been shown to promote NF1 tumor-associated pathologies in vivo. We show here that while NF1 MPNST cells have higher EGFR expression levels and are more sensitive to EGF when compared to a non-NF1 MPNST cell line, the ability of the EGFR inhibitor gefitinib to selectively inhibit NF1 MPNST cell proliferation is marginal. We also show that NF1 MPNST proliferation correlates with activated ErbB2 and can be suppressed by nanomolar concentrations of the pan-ErbB inhibitor CI-1033 (canertinib). Consequently, targeting both EGFR and ErbB2 may prove an effective strategy for suppressing NF1 MPNST tumor growth in vivo.

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Available from: Chad Hancock
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    • "EGFR, amplified in 37% (19/51) of our samples, has been suggested as a potential target in MPNST [18-20]. The comparison of the two cohorts indicated that the frequency of EGFR amplification did not differ significantly between TMUCIH samples (35%) and MD Anderson samples (40%). "
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    • "STS-26T, NF90-8, and ST88-14 MPNST cell lines were generously donated by T. Glover (University of Michigan, Ann Arbor, MI). Maintenance of these cell lines was described previously (Dilworth et al., 2008; Wojtkowiak et al., 2008). "
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