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Updated: Dec 7, 2025
Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells
Published on: September 1, 2010
The SHH/GLI signaling pathway: a therapeutic target for medulloblastoma
Ludovica Lospinoso Severini1, Francesca Ghirga2, Francesca Bufalieri1
1Department of Molecular Medicine, University of Rome La Sapienza , 00161, Rome, Italy.
Introduction:
Medulloblastoma (MB) is a heterogeneous tumor of the cerebellum that is divided into four main subgroups with distinct molecular and clinical features. Sonic Hedgehog MB (SHH-MB) is the most genetically understood and occurs predominantly in childhood. Current therapies consist of aggressive and non-targeted multimodal approaches that are often ineffective and cause long-term complications. These problems intensify the need to develop molecularly targeted therapies to improve outcome and reduce treatment-related morbidities. In this scenario, Hedgehog (HH) signaling, a developmental pathway whose deregulation is involved in the pathogenesis of several malignancies, has emerged as an attractive druggable pathway for SHH-MB therapy.
Areas Covered:
This review provides an overview of the advancements in the HH antagonist research field. We place an emphasis on Smoothened (SMO) and glioma-associated oncogene homolog (GLI) inhibitors and immunotherapy approaches that are validated in preclinical SHH-MB models and that have therapeutic potential for MB patients. Literature from Pubmed and data reported on ClinicalTrial.gov up to August 2020 were considered.
Expert Opinion:
Extensive-omics analysis has enhanced our knowledge and has transformed the way that MB is studied and managed. The clinical use of SMO antagonists has yet to be determined, however, future GLI inhibitors and multitargeting approaches are promising.
Insights
Targeting Hedgehog (HH) signaling pathways, particularly Smoothened (SMO) and glioma-associated oncogene homolog (GLI) inhibitors, shows promise for treating Sonic Hedgehog medulloblastoma (SHH-MB). Further research into these molecularly targeted therapies is crucial for improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Developmental Biology
Background:
- Medulloblastoma (MB) is a heterogeneous cerebellar tumor with four main molecular subgroups.
- Sonic Hedgehog medulloblastoma (SHH-MB) predominantly affects children and is genetically well-understood.
- Current MB therapies are aggressive, non-targeted, often ineffective, and cause significant long-term complications, necessitating targeted treatments.
Purpose of the Study:
- To review advancements in Hedgehog (HH) signaling antagonist research for SHH-MB therapy.
- To focus on Smoothened (SMO) and glioma-associated oncogene homolog (GLI) inhibitors and immunotherapy.
- To assess therapeutic potential for MB patients based on preclinical models.
Main Methods:
- Literature review of PubMed and ClinicalTrials.gov up to August 2020.
- Analysis of omics data to understand MB heterogeneity.
- Evaluation of preclinical data for HH pathway inhibitors.
Main Results:
- Extensive omics analysis has significantly advanced MB understanding and management.
- HH signaling pathway deregulation is implicated in MB pathogenesis.
- Preclinical studies validate HH antagonists, including SMO and GLI inhibitors, for SHH-MB.
Conclusions:
- Targeting the HH pathway represents a promising therapeutic strategy for SHH-MB.
- While SMO antagonist clinical utility is pending, future GLI inhibitors and multitargeting approaches are highly promising.
- Molecularly targeted therapies are essential to improve outcomes and reduce morbidities in MB patients.
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