Our Medulloblastoma (MB) projects are driven by the tumour and sequencing data that form part of the Medulloblastoma Advanced Genomics International Consortium (MAGIC). MAGIC is a SickKids-based consortium of clinicians, scientists, and pathologists from over 85 cities around the world who have collectively contributed frozen medulloblastoma samples to the genomics efforts in Toronto. 

Medulloblastoma is a not a single disease

Medulloblastoma is an embryonal tumour of the cerebellum that was thought to represent a single disease entity. Data from the Taylor Lab and others, and accepted in an international consensus statement, Taylor et. al 2011 have agreed that MB is in fact comprised of four molecularly distinct diseases that have their own epidemiology, demographics, clinical presentation, transcriptional profile, somatic genetic events, and clinical outcomes:

  1. Wnt (due to hyperactivity of Wnt signaling)
  2. Shh (due to hyperactivity of Shh signaling)
  3. Group 3
  4. Group 4
Molecular subgroups of medulloblastoma with details on demographics, clinical features, genetics and gene expression information
Molecular subgroups of medulloblastoma

Medulloblastoma is extremely heterogenic

More recently we have demonstrated that medulloblastoma is even more heterogenic than thought and may in fact be up to 12 different diseases (Cancer Cell, 2017; Nature, 2017) and that there is clinically significant heterogeneity in metastatic medulloblastomas (Nature, 2012, 2016; Nature Genetics, 2017). We have also shown that these cerebellar tumours are a disorder of early brain development, a finding which provides a proximate explanation for the peak incidence of cerebellar tumours in early childhood (Nature, 2019). 

Current medulloblastoma research

Our current research is focused on metastases because the main cause of death from MB is not the primary tumour, but rather the metastases that arise from the primary tumour. Unfortunately, MB metastases are biologically very different from their primary tumour, which means the same therapy cannot be applied to both. Despite the urgent need for treatment innovation, there are currently no drugs approved or in clinical trials for the treatment of this disease, nor are there any promising candidates. Data from our lab shows that MB can metastasize through the blood system, and that manipulation of trafficking systems can drive/attenuate metastatic phenotypes. We are now validating these systems as targets; we believe this will lead to rapidly translatable results and the development of clinical trials that would accrue patients from this underserved and highly burdened population.

Blood Dissemination of Medulloblastoma
Medulloblastoma patients show circulating tumor cells in the blood at diagnosis and these circulating tumor cells can home to the meninges to form metastases. The CCL2-CCR2 axis drives this meningeal dissemination of medulloblastoma.