Expression and clinical relevance of MET and ALK in Ewing sarcomas
| العنوان: | Expression and clinical relevance of MET and ALK in Ewing sarcomas |
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| المؤلفون: | Fleuren, E.D.G., Roeffen, M.H.S., Leenders, W.P.J., Flucke, U.E., Vlenterie, M., Schreuder, H.W.B., Boerman, O.C., Graaf, W.T.A. van der, Versleijen-Jonkers, Y.M.H. |
| المصدر: | International Journal of Cancer, 133, 427-436 International Journal of Cancer, 133, 2, pp. 427-436 |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Translational research [ONCOL 3], hemic and lymphatic diseases, Translational research Immune Regulation [ONCOL 3], Age-related aspects of cancer Quality of hospital and integrated care [ONCOL 2], Human Movement & Fatigue Quality of Care [NCEBP 10], Translational research Tissue engineering and pathology [ONCOL 3] |
| الوصف: | Contains fulltext : 118418.pdf (Publisher’s version ) (Closed access) Because novel therapeutic options are limited in Ewing sarcomas (ES), we investigated the expression, genetic aberrations and clinical relevance of MET and anaplastic lymphoma kinase (ALK) in ES and determined the relevance of targeting these receptors. MET and ALK protein expression was determined immunohistochemically in 31 (50 samples) and 36 (59 samples) ES patients, respectively. Samples included primary tumors, postchemotherapy resections, metastases and relapses. MET and ALK RTK domains were sequenced in respectively 33 and 32 tumors. Five ES cell lines were treated in vitro with the MET/ALK-inhibitor crizotinib, the ALK-inhibitor NVP-TAE684 or the MET-inhibitor cabozantinib and analyzed by MTT assays. Modest to high MET and ALK expression was detected in the majority of ES (86 and 69%, respectively). ALK expression was significantly lower in postchemotherapy resections compared to paired untreated primary tumors (p = 0.031, z = -2.310, n = 11). In primary tumors (n = 20), membranous MET expression significantly correlated with a poor overall survival (OS) (60 vs. 197 months, p = 0.014). There was a trend toward a poor event-free survival (67 vs. 111 months, p = 0.078) and OS (88 vs. 128 months, p = 0.074) in patients with highest ALK levels (n = 29). ALK or MET RTK domain aberrations were demonstrated in 5/32 (16%) and 3/33 (9%) tumors, respectively. Crizotinib (IC50 1.22-3.59 mumol/L), NVP-TAE684 (IC50 0.15-0.79 mumol/L) and cabozantinib (IC50 2.69-8.27 mumol/L) affected ES cell viability in vitro. Altogether, our data suggest that MET and ALK are potential novel therapeutic targets in ES and targeting these receptors may be of great interest to rationally design future studies in ES. |
| وصف الملف: | application/pdf |
| تدمد: | 0020-7136 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=dedup_wf_001::f0d35d88be83b4b1344cda1ad6645bd4Test http://hdl.handle.net/2066/118418Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.dedup.wf.001..f0d35d88be83b4b1344cda1ad6645bd4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00207136 |
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