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An autocrine ActivinB mechanism drives TGFβ/Activin signaling in Group 3 medulloblastoma

Morgane Morabito1,2,3,4,5, Magalie Larcher1,2,3,4,5, Florence Mg Cavalli6,7

  • 1Institut Curie, Orsay, France.

EMBO Molecular Medicine
|July 23, 2019
PubMed

Insights

Group 3 medulloblastoma (MB), a pediatric brain tumor, shows activated TGFβ/Activin signaling. Targeting this pathway with Galunisertib showed promise in preclinical models, offering a potential new therapy for this aggressive cancer.

Area of Science:

  • Pediatric Oncology
  • Molecular Biology
  • Cancer Signaling Pathways

Background:

  • Medulloblastoma (MB) is a common pediatric brain tumor with distinct molecular subgroups.
  • Group 3 MB has a poor prognosis and limited therapeutic options.
  • The TGFβ/Activin pathway's role in Group 3 MB is poorly understood.

Purpose of the Study:

  • To investigate the activation and functional relevance of the TGFβ/Activin pathway in Group 3 MB.
  • To explore therapeutic targeting of this pathway in preclinical models.

Main Methods:

  • Analysis of pathway activation in Group 3 MB patient samples.
  • Investigation of autocrine ActivinB stimulation.
  • Testing the efficacy of Galunisertib in orthotopic medulloblastoma patient-derived xenograft (PDX) models.

Main Results:

  • The TGFβ/Activin pathway is activated in a subset of Group 3 MB.
  • Autocrine ActivinB stimulation drives pathway activation in tumors with high PMEPA1 levels.
  • Galunisertib demonstrated efficacy in preclinical MB models.

Conclusions:

  • The TGFβ/Activin pathway is a relevant target in Group 3 MB.
  • Galunisertib represents a potential therapeutic strategy for targeting this pathway in medulloblastoma.
Keywords:
Smad2Smad3TGFbetaactivinmedulloblastoma

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