Medulloblastoma: experimental models and reality

Acta Neuropathol. 2017 Nov;134(5):679-689. doi: 10.1007/s00401-017-1753-3. Epub 2017 Jul 19.

Abstract

Medulloblastoma is the most frequent malignant brain tumor in childhood, but it may also affect infants, adolescents, and young adults. Recent advances in the understanding of the disease have shed light on molecular and clinical heterogeneity, which is now reflected in the updated WHO classification of brain tumors. At the same time, it is well accepted that preclinical research and clinical trials have to be subgroup-specific. Hence, valid models have to be generated specifically for every medulloblastoma subgroup to properly mimic molecular fingerprints, clinical features, and responsiveness to targeted therapies. This review summarizes the availability of experimental medulloblastoma models with a particular focus on how well these models reflect the actual disease subgroup. We further describe technical advantages and disadvantages of the models and finally point out how some models have successfully been used to introduce new drugs and why some medulloblastoma subgroups are extraordinary difficult to model.

Keywords: Group 3; Group 4; Medulloblastoma; Mouse model; SHH; WNT.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology*
  • Disease Models, Animal
  • Hedgehog Proteins / metabolism
  • Humans
  • Medulloblastoma / metabolism
  • Medulloblastoma / pathology*
  • Wnt Proteins / metabolism
  • beta Catenin / metabolism

Substances

  • Hedgehog Proteins
  • Wnt Proteins
  • beta Catenin