Johns Hopkins University

“Depleting Cancer Stem Cells by Notch Pathway Blockade in Glioblastomas”

There is emerging evidence showing that a small population of cancer stem cells (CSCs) within tumors are responsible for tumor formation and ongoing growth. This observation forms the basis of the CSC hypothesis and challenges traditional concepts in the development of cancer therapeutics. The CSC hypothesis suggests that treatments must disable or destroy CSCs within a tumor in order to achieve a cure. The goal of Dr. Fan’s project is to evaluate the potential therapeutic effects in glioblastoma (GBM) using agents that target CSCs by blocking the Notch signaling pathway.

It is well established that Notch, a protein that sits on the cell surface membrane, regulates normal neural stem cell growth and is overexpressed in GBM. In this study, Dr. Fan and his team will employ GBM neurospheres and primary cells in culture (in vitro) and in animal models (in vivo) to determine the impact of Notch pathway blockade on the proliferation and survival of CSCs in GBM as well as on tumor growth. In addition, they will identify the molecules that mediate the effects of Notch inhibitors to gain insights into the mechanism by which Notch signaling regulates CSCs.

Experimental results of this project will enhance the current understanding of CSC biology in GBM and of the potential therapeutic application of this novel class of agents in the treatment of GBM.





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