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FINDING CURES TOGETHER<sup>SM</sup>

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

Leader

Peter Dirks, MD, PhD

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

Co-leader

Samuel Weiss, PhD

Samuel Weiss, PhD
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:

$11.7 million

Principals

Michael David Taylor, MD, PhD, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning

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

Cheryl Hillock Arrowsmith, PhD, University of Toronto

Michael William Salter, MD, PhD, The Hospital for Sick Children, Peter Gilgan Centre for Research & Learning

Marco Antonio Marra, Genome Sciences Centre, BC Cancer Agency

Mathieu Lupien, PhD, Princess Margaret Cancer Centre Research University Health Network

Amy Anne Caudy, PhD, Donnelly Centre for Cellular and Biomolecular Research, University of Toronto

Trevor John Pugh, PhD, Princess Margaret Cancer Centre

Gary David Bader, PhD, The Donnelly Centre, University of Toronto

Michael David Tyers, PhD, Institute for Research in Immunology and Cancer, University of Montreal

Advocates

Wendy Marie Durigon, founder & fundraiser, Jessica's Footprint

Warren Phillip Mason, medical director, Princess Margaret Cancer Centre, University Health Network

Eric Bouffet, director, Paediatric Brain Tumour Program, The Hospital for Sick Children