Signaling pathway and molecular subgroups of medulloblastoma

Int J Clin Exp Pathol. 2013 Jun 15;6(7):1211-22. Print 2013.

Abstract

Medulloblastoma (MB) is the most common malignant brain tumor in children. Although multimodality treatment regimens including surgery, radiotherapy and chemotherapy have greatly improved disease outcome, about one-third of MB patient remains incurable, and many long-term survivors are suffered from deleterious effects due to aggressive treatment. Understanding the signaling pathways and the genetic mechanisms contributed to MB development would be the key to develop novel therapeutic treatment strategies for improving survival and outcome of MB. In this review, we discuss the biological signaling pathways involved in MB pathogenesis. We also go through the current international consensus of four core MB subgroups namely, SHH, WNT, Group 3, and Group 4. This is adopted based on the knowledge of genomic complexity of MB as analyzed by recent high-throughput genomic technology. We talk about immunohistochemistry assays established to determine molecular subgroup affiliation. In the last part of review, we discuss how identification of molecular subgroups is going to change our routine disease diagnosis and clinical management.

Keywords: Medulloblastoma; molecular subgroups; signaling pathway.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Cerebellar Neoplasms / classification
  • Cerebellar Neoplasms / drug therapy
  • Cerebellar Neoplasms / genetics*
  • Cerebellar Neoplasms / metabolism
  • Cerebellar Neoplasms / pathology
  • Drug Resistance, Neoplasm
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Genomics / methods
  • Humans
  • Medulloblastoma / classification
  • Medulloblastoma / drug therapy
  • Medulloblastoma / genetics*
  • Medulloblastoma / metabolism
  • Medulloblastoma / pathology
  • Molecular Targeted Therapy
  • Patient Selection
  • Phenotype
  • Precision Medicine
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor