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Funded Grants

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Genetic and therapeutic dependencies in SHH driven childhood medulloblastoma

Project Overview

Medulloblastoma is the most common malignant brain tumour of childhood, affecting 60-80 Canadian children per year. The treatment for medulloblastoma comprises surgery, followed by radiation to the entire brain and spinal cord, and high doses of non-specific chemotherapy. Despite such aggressive treatment, survival is only around 60%, with survivors left with long-term side effects of radiation to the developing brain. As such, we urgently need new personalized therapies that are less toxic and more effective.

Although classically thought of as one tumour entity, applying next generation genomics it is now known that medulloblastoma is actually comprised of multiple different diseases, where the molecular “subgroup” can predict outcome with a high degree of accuracy. The WNT subgroup have an excellent prognosis and are candidates for reductions in therapy intensity, but one of the groups accounting for a high proportion of relapses is a subset of tumours termed TP53-mutant SHH medulloblastoma. This subset of patients have a very poor survival, and need to be prioritized for new therapies.

This proposal will attempt to understand why this group of very high risk medulloblastoma relapse in light of our current treatments. We will employ a technique called functional genomics, where we will try to understand which genes in the tumour are responsible for radiation resistance, and using this information we will try to develop new therapies which allow radiation to work more effectively. We will also study normal brain cells that give rise to SHH medulloblastoma to understand any new insights in the context of the developing nervous system. The overarching goal of this proposal is to identify new personalized, more effective and less toxic treatments for this very high-risk group of childhood brain tumours. This will allow survivors to have an improved quality of life, and lessen the devastating effects of radiation therapy.

Impact

Treatment for medulloblastoma has remained unchanged since the 1980s; it’s invasive, it’s toxic, and given that most of these tumours occur in young children, it brings heartbreaking, lifelong side-effects. In the last decade, scientists have identified four distinct types of medulloblastoma tumours, each with unique growth mechanisms and clinical outcomes. Dr. Ramaswamy and his research team focused on the most high-risk, recurring tumour types, given the pressing need for new ways to treat them. He and his team identified an Achilles heel in these tumours to target therapeutically, which promises to both increase the efficacy of treatment and reduce the long-term toxicity for this hard-to-treat tumour.

Principal Investigator

Vijay Ramaswamy , The Hospital for Sick Children

Partners and Donors

Alvin Segal Family Foundation

Project Complete

Genetic and therapeutic dependencies in SHH driven childhood medulloblastoma

  • Grant Type

    Capacity building grants

  • Area of research

    Cancer

  • Disease Area

    Brain Cancer

  • Competition

    Future Leaders in Canadian Brain Research

  • Province

    Ontario

  • Start Date

    2021

  • Total Grant Amount

    $100,000

  • Health Canada Contribution

    $50,000

Contact Us

1200 McGill College Avenue
Suite 1600, Montreal, Quebec
H3B 4G7

+1 (514) 989-2989 info@braincanada.ca

Please note all online donations will receive an electronic tax receipt, issued by Brain Canada Foundation.

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Territorial acknowledgement

The offices of Brain Canada Foundation are located on the traditional, ancestral territory of the Kanien'kehá:ka Peoples, a place which has long served as a site of meeting and exchange amongst nations. We honour and pay respect to elders past, present and emerging, and dedicate ourselves to moving forward in the spirit of partnership, collaboration, and reconciliation. In our work, we focus our efforts on the Truth and Reconciliation Commission’s Calls to Action, particularly those that pertain to improving health for Indigenous Peoples and that focus on advancing our own learning on Indigenous issues.

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