التفاصيل البيبلوغرافية
| العنوان: |
Hepatocyte growth factor (HGF) autocrifle activation predicts sensitivity to MET inhibition in glioblastoma. |
| المؤلفون: |
Qian Xi, Bradley, Robert, Liang Kang, Koeman, Julie, Libera Ascierto, Maria, Worschech, Andrea, De Giorgi, Valeria, Wang, Ena, Kefene, Lisa, Yanli Su, Essenburg, Curt, Kaufman, Dafna W., DeKoning, Tom, Enter, Mark A., Rourke, Timothy J. O, Marincola, Francesco M., Vande Woude, George F. |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 1/10/2012, Vol. 109 Issue 2, p570-575, 6p |
| مصطلحات موضوعية: |
HEPATOCYTE growth factor, GLIOBLASTOMA multiforme, ONCOGENES, CYTOGENETICS, PLATELET-derived growth factor, EPIDERMAL growth factor receptors |
| مستخلص: |
Because oncogene MET and EGF receptor (EGFR) inhibitors are in clinical development against several types of cancer, including glioblastoma, it is important to identify predictive markers that indicate patient subgroups suitable for such therapies. We investigated in vivo glioblastoma models characterized by hepatocyte growth factor (HGF) autocrine or paracrine activation, or by MET or EGFR amplification, for their susceptibility to MET inhibitors. HGF autocrine expression correlated with high phospho-MET levels in HGF autocrine cell lines, and these lines showed high sensitivity to MET inhibition in vivo. An HGF paracrine environment may enhance glioblastoma growth in vivo but did not indicate sensitivity to MET inhibition. EGFRvIII amplification predicted sensitivity to EGFR inhibition, but in the same tumor, increased copies of MET from gains of chromosome 7 did not result in increased MET activity and did not predict sensitivity to MET inhibitors. Thus, HGF autocrine glioblastoma bears an activated MET signaling pathway that may predict sensitivity to MET inhibitors. Moreover, serum HGF levels may serve as a biomarker for the presence of autocrine tumors and their responsiveness to MET therapeutics. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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