The role of AXL and the in vitro activity of the receptor tyrosine kinase inhibitor BGB324 in Ewing sarcoma.
作者： Emmy D.G. Fleuren , Melissa H.S. Hillebrandt-Roeffen , Uta E. Flucke , D. Maroeska W.M. te Loo , Otto C. Boerman
关键词: Receptor tyrosine kinase 、 In vitro 、 Doxorubicin 、 Pathology 、 Sarcoma 、 Vincristine 、 Cancer research 、 Biology 、 Viability assay 、 GAS6 、 Cell culture
摘要: New targets for Ewing sarcoma (ES) patients are urgently needed. Therefore, we investigated the expression and genetic aberrations of oncogenic receptor tyrosine kinase (RTK) AXL in ES determined efficacy targeting on cell viability migration. First, Gas6 (ligand) mRNA was by RT-PCR 29 samples. Low, medium high observed 31% (n = 9), 48% 14) 21% 6) abundantly present all specimens. We next tested protein immunohistochemically 36 tumors (primary, post-chemotherapy, metastasized relapsed samples) from 25 patients. 17% 6), 19% 7) 36% 13) In primary 15), correlated significantly with a worse overall survival compared to lower (61 vs. 194 months, p 0.026). No were detected RTK domain 29). The AXL-inhibitor BGB324 affected (IC50 0.79-2.13 μmol/L) migratory potential lines vitro 5-6). chemosensitized chemotherapy-resistant ES-4 cells vincristine doxorubicin. These data suggest that is novel, druggable therapeutic target ES.
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