GET THE APP

Dissecting the therapeutic determinants of MET inhibition: HGF-au | 21146
Journal of Cell Science & Therapy

Journal of Cell Science & Therapy
Open Access

ISSN: 2157-7013

+44 1300 500008

Dissecting the therapeutic determinants of MET inhibition: HGF-autocrine activation predicts sensitivity to MET inhibitor in Glioblastoma


International Conference & Exhibition on Cell Science & Stem Cell Research

29 Nov - 1 Dec 2011 Philadelphia Airport Marriott, USA

Qian Xie

Scientific Tracks Abstracts: J Cell Sci Ther

Abstract :

Due to its invasive nature, glioblastoma (GBM) is the most aggressive brain cancer. Hepatocyte growth factor (HGF) binds to MET tyrosine kinase receptor and induces invasive tumor growth. As MET inhibitors are entering clinical trials against several types of cancer including GBM, it is compelling to identify therapeutic determinants which could indicate which patient subsets are suitable for this therapy. We investigated in vivo three types of GBM models for their sensitivity to MET or EGFR inhibitors: 1) Tumors sustained by an HGF- autocrine loop; 2) tumors displaying paracrine HGF tumor growth; and 3) tumors with MET polysomy and EGFR amplifi cationOf the three tumor types, we observed that HGF- autocrine activation correlates with p-MET levels in the HGF autocrine GBM cell lines, which in turn are extremely sensitive to MET inhibition in vivo . Moreover, serum HGF levels in HGF-autocrine loop GBM xenograft s correlate with MET inhibition. Paracrine HGF can enhance GBM growth in vivo , but they were not signifi cantly sensitive to MET inhibition. In type three tumors, EGFR VIII amplifi cation predicted sensitivity to erlotinib, but MET polysomy in the same tumor did not display MET activity and the cells did not show sensitivity to MET inhibition. We conclude that HGF- autocrine activation GBM tumors bear an activated MET signaling pathway that may be used to predict sensitivity to MET inhibitors in GBM patients. However, targeting MET alone may not be suffi cient for treating GBM and the combination of MET with other RTK inhibitors, especially EGFR inhibitors should be considered.

Biography :

Dr. Xie completed her doctorate in Oncology from Fudan University in China. She then joined the Laboratory of Molecular Oncology (LMO) at Van Andel Research Institute as a postdoctoral fellow. She has been continuously working on the MET signaling pathway, focusing mainly on brain cancer. Dr. Xie is currently a Senior Research Scientist in the (LMO) under the direction of Dr. George Vande Woude; her major research goal is to understand the mechanism of brain cancer malignancy and to develop novel strategies particular with MET inhibitors to target glioblastoma

Top