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Paediatric therapeutic development workshop on medulloblastoma

Claudia Montiel Equihua1, Joseph S Baxter1, Jan J Molenaar2

  • 1LifeArc, London, UK.

British Journal of Cancer
|July 9, 2026
PubMed

Insights

Developing new medulloblastoma therapies is crucial. The workshop prioritized targeting SRC, c-MYC/MYCN, and WNT pathways, alongside B7-H3 for CAR T-cell and ADC approaches, to improve survival and reduce side effects.

Area of Science:

  • Pediatric Oncology
  • Cancer Therapeutics Development
  • Molecular Oncology

Background:

  • Medulloblastoma survival rates vary significantly by subtype, with high-risk groups facing poor prognoses (<10% survival).
  • Survivors of medulloblastoma often experience severe long-term side effects, highlighting the need for less toxic treatments.
  • Specific molecular subgroups, including SHH-medulloblastoma (MYCN amplified or TP53 mutated) and Group 3 medulloblastoma (c-MYC amplified), represent high-risk populations requiring targeted therapies.

Purpose of the Study:

  • To identify high-priority therapeutic strategies for medulloblastoma based on the Paediatric Therapeutic Development Workshop.
  • To outline innovative approaches for both poor-prognosis and good-prognosis medulloblastoma subtypes.
  • To guide the development of novel therapeutics and combination strategies to improve patient outcomes and reduce treatment toxicity.

Main Methods:

  • Consensus-based recommendations from the Paediatric Therapeutic Development Workshop on medulloblastoma.
  • Review of pre-clinical evidence and biological understanding to inform therapeutic development.
  • Discussion of potential combination therapies, including PARP-1, CHK1/2, CDK9, and ATR inhibitors.

Main Results:

  • High priority is placed on targeting SRC with degraders and inhibiting c-MYC/MYCN functions in poor-prognosis medulloblastoma.
  • An innovative approach involves using radiolabeled theranostic antibodies for WNT-medulloblastoma to reduce toxicity.
  • B7-H3 is identified as a promising target for CAR T-cell and Antibody-Drug Conjugate (ADC) therapies.

Conclusions:

  • Targeting specific molecular vulnerabilities in medulloblastoma subtypes is essential for improving survival.
  • Combination therapies, such as CNS-penetrant inhibitors, require rigorous pre-clinical evaluation before early-phase trials.
  • Future early-phase clinical studies should be international, incorporate novel designs for small patient cohorts, and integrate correlative biological studies.

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