The ability of malignant gliomas to disperse within normal brain ultimately renders ineffective all of our current therapies for this tumor. This invasive propensity is further stimulated by antiangiogenics, which have entered the mainstream of glioma therapeutics. Unfortunately, treatments designed to block this invasive phenotype do not produce universal or durable response, which underscores the need to find new ways of targeting brain dispersion by this tumor. In our prior work, we established that the molecular motor non-muscle myosin II (NMMII) is an essential component of the glioma invasion apparatus. In this application, we will examine the roles of NMMII in driving glioma invasion and the efficacy of targeting NMMII in blocking the invasive phenotype of malignant gliomas in a set of realistic and robust preclinical models of glioblastoma. Results from these translational studies will be combined with combination therapy studies in our pre-clinical models in order to identify potential synergy between NMMII inhibitors and anti-angiogenic and radiation therapy.

Public Health Relevance

The ability of gliomas to invade brain limits all the current therapies for this disease, and this highlights the need to develop new methods to block brain tumor invasion. In this application, we propose that the molecular motor NMMII represents such a target. In this study, we will critically examine how NMMII drives glioma dispersion and how it can be specifically and effectively targeted.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01NS073610-03
Application #
8730238
Study Section
Clinical Neuroimmunology and Brain Tumors Study Section (CNBT)
Program Officer
Fountain, Jane W
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Cleveland Clinic Lerner
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
City
Cleveland
State
OH
Country
United States
Zip Code
44195
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