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.

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