The studies we are proposing will compare epidermal growth factor receptor (EGFR) targeted liposome- formulated topotecan (EGFR-LFT) vs. non-targeted liposome-formulated topotecan (NT-LFT) for efficacy in treating orthotopic glioblastoma (GBM) xenografts. As part of this research, we will also address GBM EGFR status (EGFR-amplified vs. non-amplified) and LFT route of delivery (direct intracranial administration vs. systemic administration) as factors that influence LFT therapeutic efficacy. Liposome formulations of topotecan will be tested as single agents as well as in combination with radiation. At the end of the requested period of support, this project will address whether systemic delivery of LFT is a viable strategy for treating brain tumors, and whether EGFR targeted delivery of LFT should be specifically used for treating tumors that have amplified EGFR. More generally, this project will address whether EGFR targeting of liposome-formulated chemotherapy should be further developed for use in clinical practice of treating GBM.

Public Health Relevance

The studies proposed in this application will determine whether a molecular characteristic in a highly malignant type of brain tumor can be exploited for improving the delivery and anti-tumor effect of a commonly used cancer therapeutic. The results of these studies will have important implications for improving the delivery and efficacy of a large number of anti-cancer agents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS065819-02
Application #
7843605
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Fountain, Jane W
Project Start
2009-05-15
Project End
2011-10-30
Budget Start
2010-05-01
Budget End
2011-10-30
Support Year
2
Fiscal Year
2010
Total Cost
$193,125
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