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Research Grants

 

Personalized Therapy for Glioma using Notch and Akt Inhibition
Led by Xing Fan, MD PhD at the Department of Neurology at Regents of the University of Michigan

The goal of this proposal is to examine the efficacy of personalized therapy to adult glioblastoma (GBM) based on targeting the signaling pathways that regulate cancer stem-like cells (CSLCs) based on Notch and Akt pathway inhibition in a pre-clinical mouse model.

CSLCs are thought to be critical for the long-term growth of GBM. They are at least partially spared by traditional chemo- and radiation-
therapies, and finding new treatments which can target CSLCs may be critical for improving patient survival. With funds from a recent search grant from VABC, Dr. Fan’s lab recently demonstrated that Notch pathway blockade by gamma-secretase inhibitor (GSI) depleted CSLCs, inhibited neurosphere growth and propagation, and prolonged the survival of mice bearing the intracranial xenografts. We also found that Akt inhibitor perifosine can reduce GBM neurosphere growth.

However, difference in the genetic background of GBM may result in different responses to GSI or perifosine. This study will examine whether GBM with one type of background responds better to GSI treatment while GBM with another type of background responds better to perifosine. Dr. Fan will identify GBM patients subsets that will benefit from Notch pathway inhibition or Akt inhibitions based on individual genetic backgrounds.

Success in this proposal will enhance understanding of tumor biology and have significant clinical relevance for treatment of GBM.

Pictured: Dr. Fan’s Lab Team
Front row (from left to right): Mikel Gurrea, Nicole Garcia, Jessica Crowley, Christina Lineback, Mark Costello, Libby Talsma, and Callie Flack.
Rear row (from left to right): Xiaobing He, Thant Zhu, Peng Xu, Xing Fan, and Mary Soules.


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.

 

 

 

 
Voices Against Brain Cancer is a not-for-profit public charity recognized by the IRS under 501 (c) (3)