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http://purl.uniprot.org/citations/23867124http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23867124http://www.w3.org/2000/01/rdf-schema#comment"

Background

Rhabdomyosarcoma (RMS) is an aggressive soft tissue tumour mainly affecting children and adolescents. Since survival of high-risk patients remains poor, new treatment options are awaited. The aim of this study is to investigate anaplastic lymphoma kinase (ALK) and insulin-like growth factor-1 receptor (IGF-1R) as potential therapeutic targets in RMS.

Patients and methods

One-hundred-and-twelve primary tumours (embryonal RMS (eRMS)86; alveolar RMS (aRMS)26) were collected. Expression of IGF-1R, ALK and downstream pathway proteins was evaluated by immunohistochemistry. The effect of ALK inhibitor NVP-TAE684 (Novartis), IGF-1R antibody R1507 (Roche) and combined treatment was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in cell lines (aRMS Rh30, Rh41; eRMS Rh18, RD).

Results

IGF-1R and ALK expression was observed in 72% and 92% of aRMS and 61% and 39% of eRMS, respectively. Co-expression was observed in 68% of aRMS and 32% of eRMS. Nuclear IGF-1R expression was an adverse prognostic factor in eRMS (5-year survival 46.9 ± 18.7% versus 84.4 ± 5.9%, p=0.006). In vitro, R1507 showed diminished viability predominantly in Rh41. NVP-TAE684 showed diminished viability in Rh41 and Rh30, and to a lesser extent in Rh18 and RD. Simultaneous treatment revealed synergistic activity against Rh41 and Rh30.

Conclusion

Co-expression of IGF-1R and ALK is detected in eRMS and particularly in aRMS. As combined inhibition reveals synergistic cytotoxic effects, this combination seems promising and needs further investigation."xsd:string
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http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/author"Suurmeijer A.J."xsd:string
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/author"van der Graaf W.T."xsd:string
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/author"de Bont E.S."xsd:string
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/author"van der Heijden G."xsd:string
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/author"van der Laak J.A."xsd:string
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/author"Flucke U.E."xsd:string
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/author"Roeffen M.H."xsd:string
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/author"Versleijen-Jonkers Y.M."xsd:string
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/author"van Gaal J.C."xsd:string
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/name"Eur J Cancer"xsd:string
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/pages"3462-3470"xsd:string
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/title"Simultaneous targeting of insulin-like growth factor-1 receptor and anaplastic lymphoma kinase in embryonal and alveolar rhabdomyosarcoma: a rational choice."xsd:string
http://purl.uniprot.org/citations/23867124http://purl.uniprot.org/core/volume"49"xsd:string
http://purl.uniprot.org/citations/23867124http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/23867124
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