Amplification of EGFR was the first gene alteration identified in the most common and most malignant of primary brain tumors, glioblastoma (GBM). In spite of nearly 2 decades of GBM-EFGR research, and the substantial body of information that has accumulated from the related investigations, little effort has been directed to the development of an in vivo system for facilitating studies of the molecular biology and therapeutic targeting of highly-expressed Egf receptor in GBMs with amplified EGFR. This proposal is for the purpose of addressing this deficiency, and for using the model(s) derived from this work for addressing fundamental issues involving EGFR amplification in GBM. The model we are developing and characterizing, serially-transplantable GBM xenograft lines that maintain EGFR amplification, will be used to accomplish the following specific aims:
Specific Aim 1 : Identify changes in the molecular and tumor biological properties associated with the establishment of cell lines from GBM xenograft with EFGR amplification.
Specific Aim 2 : Confirm the preliminary observations of an in vivo relationship between EGFR amplification and elevated PLCy phosphorylation, and identify molecular and tumor biologic consequences of this relationship.
Specific Aim 3 : Determine and intrepret, with respect to EFGR amplification status, the in vivo effects of small molecule inhibitors of Egf receptor on the orthotopic growth, invasion, vasularization, and apoptotic response of GBM xenografts. In addition to that which we accomplish by implementing the research plan described herein, we anticipate that the resources that are developed and distributed in association with this project will allow other groups a better opportunity to achieve their own EFGR-related research objectives. These xenograft lines will, therefore assist other members of the research community in focusing a sizeable repertoire of approaches and disciplines on the consequences of this gene alteration, and to thoroughly investigate the clinical potential of therapies directed against Efg receptor.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS049720-05
Application #
7228952
Study Section
Special Emphasis Panel (ZRG1-BDCN-B (01))
Program Officer
Fountain, Jane W
Project Start
2004-08-01
Project End
2009-03-31
Budget Start
2007-04-01
Budget End
2008-03-31
Support Year
5
Fiscal Year
2007
Total Cost
$303,657
Indirect Cost
Name
University of California San Francisco
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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