Identification of the c-met receptor as a novel target for the treatment of EGFRvIII-expressing glioblastoma

CHED 212

Ryan A Flynn, raflynn5@mit.edu1, Paul Huang1, Frank B Furnari2, Webster K Cavenee2, and Forest M White1. (1) Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, (2) Ludwig Institute for Cancer Research, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093
EGFRvIII is a truncated mutant of the epidermal growth factor receptor (EGFR) which is implicated in glioblastoma multiforme. Phosphoproteomic analysis of U87MG glioblastoma cell line expressing EGFRvIII has provided a systems view of critical downstream signaling components involved in tumor progression. Clustering of the phosphoproteomic data revealed that phosphorylation sites on the c-Met receptor are highly responsive to EGFRvIII expression levels. The c-Met receptor may represent an alternative therapeutic candidate to overcome EGFR kinase inhibitor resistance. EGFRvIII expressing cells were treated with SU11274, a c-Met specific inhibitor. This treatment, either singly or in combination with AG1478, led to a dose-dependent decrease in cell growth and increase in apoptosis. In addition, the previously reported chemoresistance of EGFRvIII expressing cells to cisplatin was overcome by co-treatment of SU11274. Our data indicates that the c-Met receptor may represent an alternative target in the treatment of EGFRvIII positive tumors.
 

Undergraduate Research Poster Session
2:30 PM-4:30 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Chemical Education

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007