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SU2C Canada Cancer Stem Cell Dream Team: Targeting Brain Tumour Stem Cell Epigenetic and Molecular Networks

Leader


Peter Dirks, MD, PhD

Senior Scientist and Neurosurgeon
Garron Family Chair in Childhood Cancer Research
The Hospital for Sick Children, Toronto
Professor of Surgery and Molecular Genetics
University of Toronto
 
 

Co-leader


Director, Hotchkiss Brain Institute
Professor, Departments of Cell Biology and Anatomy, and
Physiology and Pharmacology
Cumming School of Medicine
University of Calgary


 

Overview

The team will focus on glioblastomas in adults and children and on posterior fossa ependymomas of infants, both of which have a dismal outlook for patients and for which treatment options are limited. Less than 10 percent of adults are living five years after a glioblastoma diagnosis. In children, cancers of the brain and central nervous system are the No. 1 pediatric cancer killer, even though leukemia is the more common pediatric cancer.
 
Researchers have found that these cancers contain brain tumour stem cells (BTSCs). While similar to nerve stem cells that mature during normal brain development, abnormal programming in BTSCs allows them to drive tumour relapse (or the ability of the tumours to grow back again) and drug resistance. The Dream Team’s goal is to understand the abnormalities in BTSCs so that they can identify vulnerabilities that can be used to develop new drugs that are effective against brain cancers.
 
To achieve this goal, the Dream Team will take a three-pronged approach to understanding and targeting brain cancer stem cells that resist treatment and fuel tumour regrowth. Their first approach is to perform detailed analysis of BTSCs taken from 70 different glioblastomas or ependymomas and grown in the laboratory. They will use cutting-edge technology to understand the full biological profile of these cells – from changes in the cells’ genetic codes to epigenetic programs that control when genes are turned on or off and alterations in the way the cells metabolize nutrients.
 
The Dream Team’s second approach will be to screen a collection of chemicals on the same BTSCs for potential new drugs and drug combinations that are effective against these cells. Finally, while they are learning about the biology of BTSCs and screening for new compounds, the Dream Team will test five new potential drugs that they have already identified as very promising by tests performed in laboratory mice to find out which drugs or drug combinations might kill glioblastomas or ependymomas. The Dream Team hopes to bring new drugs for brain cancer into clinical trials in the third and fourth years of their research funding.
 

Amount of Funding

11,700,000 CAD over a four-year period

 

Principals

Michael D. Taylor, MD, PhD, FRCSC The Hospital for Sick Children

Nada Jabado, MD, PhD Research Institute of the McGill University Health Centre

Cheryl H. Arrowsmith, PhD University of Toronto

Michael Salter, MD, PhD, FRSC The Hospital for Sick Children

Marco Antonio Marra, PhD BC Cancer Agency

Mathieu Lupien, PhD Princess Margaret Cancer Centre

Amy A. Caudy, PhD University of Toronto

Trevor J. Pugh, PhD, FACMG Princess Margaret Cancer Centre

Gary D. Bader, PhD University of Toronto

Michael D. Tyers, PhD University of Montreal

 

Advocate

Wendy Marie Durigon, Jessica's Footprint  

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