Brain Cancer Translational Research Initiative

Co-leads

Clinical: Dr. Peter Dirks, Hospital for Sick Children (SickKids)
Scientific: Dr. Michael Taylor (SickKids)

Goal

The goal of the Brain Cancer TRI is to investigate the cellular and genetic differences (heterogeneity) of Medulloblastoma (MB) and Glioblastoma Multiforme (GBM) in children and adults in order to uncover a new understanding of the biology of brain cancer and use this knowledge to develop new treatments for patients.

Problem

Nearly 3,000 Canadians are newly diagnosed with brain cancer each year. Brain tumours are some of the most difficult cancers to treat, with survival for GBM, the most common type of primary malignant tumour, averaging about one year. There remains a lack of effective therapies currently available for patients, many of whom are children and young adults (and for whom long-term side effects can be extremely damaging). There is an urgent need to build on important recent insights into tumour classification and tumour biology, many of which were made in Ontario, and to identify why treatment is failing.

Approach

At first glance heterogeneity could be seen as a barrier to effective therapies, because targeted agents effective in one tumour are unlikely to be effective in another patient and similarly, some agents might be effective in one part of the tumour’s life cycle (e.g., at diagnosis), but not at a later time point (e.g., recurrence) or after the tumour has spread to a different part of the body. However, initial data from the work of Drs. Dirks and Taylor offer very strong evidence that in many cases recurrence and metastases follow pathways that ‘converge’ on the same gene or molecular pathway across individuals in a process of parallel evolution. As such, tumour heterogeneity could actually be a major opportunity for the development of new treatments. The OICR Brain Cancer TRI brings together a group of clinicians and scientists who will undertake in-depth, integrated analysis of bulk patient tumour samples, as well as individual tumour cells over time, linking data to patient phenotypes, outcomes, and treatment responses, as well as testing key targets and combinations of targets in experimental systems to ensure effective translation to patients.

Specifically, the TRI focuses on three key areas:

  1. Multimodal investigation of intratumoural heterogeneity in order to identify drivers of tumour initiation, recurrence and metastases.
  2. Test potential drivers in model systems.
  3. Test a novel clinical approach to treating GBM using an Ontario-developed viral-based immunotherapy, which is less sensitive to tumour heterogeneity.

Patient impact

Ontario has extensive expertise in pediatric and adult brain cancer research and provides world-class treatment for patients. The insight gained from the Brain Cancer TRI will lead to innovative new targeting strategies to selectively kill off the most difficult source of tumour growth and propagation in both primary as well as metastatic and relapsed tumours, ultimately improving treatment and reducing side effects for both children and adults in one of the most complex and deadly types of cancer.