Treatment of Glioblastoma Intracranial Xenografts by Notch Inhibition
Led by Xing Fan, MD PhD at the Department of Neurology at Regents of the University of Michigan

The Peter Philbrick Memorial Grant

There is emerging evidence showing that a small population of cancer stem cells within brain tumors, including glioblastomas, are responsible for tumor formation and ongoing tumor growth. The Notch Signaling Pathway is important for cell to cell communication, which involves genetic regulation mechanisms that control multiple cell growth during embryonic and adult life. It has been shown that the Notch Signaling Pathway regulates normal stem cells in the central nervous system.

Notch signaling for some reason malfunctions in many cancers. This study hypothesizes that a combination of inhibitors of Notch signaling and radiation therapy will enhance the depletion of cancer stem cells, and improve the treatment of glioblastoma.

Update, 2009

Dr. Fan reports that the project is on schedule and the lab has finished the Notch inhibitor treatment in GBM intracranial xenografts and combination with down stream target Akt inhibitor treatment in vitro. They are currently working on combination treatment in vivo.

He has found notch inhibition prevents GBM neurosphere growth in vitro and propagation in vivo. So far, there have been no unexpected results and Dr. Fan plans to publish the study's results in a scientific peer-reviewed journal.

Update, 2010

Dr. Fan reports they have identified 16 glioblastoma patients that may be benefit from Notch inhibitor or Akt inhibitor treatment and will select at least four of them for the function studies in vitro based on their genetic background (two from PTEN wild type and two from PTEN mutant GBM patients).

They have finished the in vivo experiments in two GBM neurosphere lines derived from GBM patients (one from PTEN wild type and one from PTEN mutant GBM patient). They also have established several primary GBM intracranial xenografts and will select at two of them for the function studies in vivo based on their genetic background (one from PTEN wild type and one from PTEN mutant GBM patient).

Click here to download a PDF of Dr. Fan's Research Publication in "Stem Cells" Journal
VABC's support is acknowledged on page 15

Click here to download a PDF of Dr. Fan's Research Publication in the "Journal of Proteome Research"

Update, 2011

Click here to download a PDF of Dr. Fan's Research Publication in "Cancer Research" Journal

Click here for a full list of research grants funded by Voices Against Brain Cancer.