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2006
Santosh Kesari, M.D., Ph.D.
Dana-Farber Cancer Institute
Notch Inhibition in Malignant Gliomas
Glioblastoma is the most common and lethal subtype of glioma and despite numerous treatment modalities, the historical median survival for patients has only ranged from nine to 15 months. Over the years, many details have been elucidated regarding the abnormal molecular pathways in gliomas and the recent identification of "tumor stem cells" in human gliomas raises the possibility that brain cancer may be due to aberrant development processes in adult neural stem cells.
One of the important neuro-developmental programs, the Notch pathway, is increasingly considered to play a role in many types of cancers, including gliomas and is thought to be critical in regulating multiple steps in neural and glial development. Preliminary laboratory data suggests that a novel Notch inhibitor can inhibit the growth of glioma cell lines suggesting that inhibiting this pathway may well be useful in stopping growth of brain tumors.
Thus, the goal of this translational study is to evaluate the efficacy of Notch inhibitors in glioma models and to understand the mechanism of growth inhibition. This research will offer insights into how normal neuro-developmental mechanisms can be subverted to form brain tumors and how they can be targeted for eradication.
The overarching goal of this study is to provide the pre-clinical evidence to quickly initiate a Phase I/II clinical trail in patients with glioblastomas.
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