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

Samuel Weiss, PhD
Co-leader

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

Peter Dirks, MD, PhD
Leader

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

Overview

Malignant brain tumors remain deadly, incurable diseases. 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. Researchers previously discovered that at the root of these tumors lies a relatively small population of cells, known as brain tumor cancer stem cells (BTSCs) that are able to grow the whole tumor and are skilled at evading therapy. When patients undergo treatment, this tumor subpopulation survives the therapy and regrows the tumor, causing a relapse in the patients.

To characterize these cells, the team is taking a three-tiered approach: 1) BTSCs from 70 patients will be analyzed use cutting-edge technology to understand their full biological profile; 2) a panel of drugs will be tested on these tumors to find promising candidates; and 3) drug testing will be performed in pre-clinical mouse models to predict efficacy in human patients.

Taking a multi-disciplinary approach, the team will provide new insights into BTSC biology, providing a promising avenue to solving a long-standing problem.

Progress to Date

Using the new gene editing tool called CRISPR/Cas9, the Dream Team has identified genes that are critical to the persistence of glioblastomas. The team has also shown that already available inhibitory drugs for some of these genes can also be used against brain tumor stem cells, thus fast-tracking the process of identifying potential treatments that can be tested in the clinic.

Amount of Funding

$11.7 million

Principals

  • Michael David Taylor, MD, PhD, The Hospital for Sick Children, Peter Gilgan Centre for Research and 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 and 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 and fundraiser, Jessica’s Footprint
  • Warren Phillip Mason, medical director, Princess Margaret Cancer Centre, University Health Network
  • Eric Bouffet, director, Pediatric Brain Tumor Program, The Hospital for Sick Children