ePoster

MITOCHONDRIAL METABOLISM INHIBITION AS A NEW THERAPEUTIC STRATEGY AGAINST MEDULLOBLASTOMA

Irene Chavarría Cubeland 4 co-authors

Traslational Research Unit, Hospital Universitario Miguel Servet, IIS Aragón

FENS Forum 2026 (2026)
Barcelona, Spain
Board PS06-09PM-019

Presentation

Date TBA

Board: PS06-09PM-019

Poster preview

MITOCHONDRIAL METABOLISM INHIBITION AS A NEW THERAPEUTIC STRATEGY AGAINST MEDULLOBLASTOMA poster preview

Event Information

Poster Board

PS06-09PM-019

Abstract

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Although prognosis has significantly improved, 25–30% of patients still die from the disease. Our work focuses on Group 3 (G3) and Group 4 (G4), the subtypes with the poorest prognosis and highest metastatic rates. Our initial studies suggested that Medulloblastoma Cancer Stem Cells (MB-CSCs), a chemoresistant subpopulation implicated in metastasis and recurrence, rely on mitochondrial metabolism for proliferation and survival. Thus, we hypothesized that mitochondrial inhibition would improve treatment efficacy in G3 (D425, MB002) and G4 (CHLA‑01‑Med) cellular models. First, we screened different metabolic inhibitors and found that the respiratory complex I inhibitor metformin selectively induced cell death in MB-CSC enrichment models and reduced self‑renewal in vitro, although it did not consistently improve survival in vivo. Next, we evaluated triptolide, which significantly decreased stem cell frequency, improved overall survival in vivo, and showed synergistic activity with chemotherapy. In parallel, and considering the inconsistency between in vitro and in vivo results, we are developing a novel MB‑on‑chip platform that better recapitulates the tumor microenvironment and provides a more predictive system for assessing therapeutic responses. Our results support mitochondrial inhibition, using the compound triptolide, as a promising strategy to target MB‑CSCs, improving MB treatment. Our study represents a proof-of-concept for the value of medulloblastoma‑on‑chip model as a novel technological approach that may enhance the translational relevance of in vitro assays and ultimately serve as a platform for more reliable drug screening in MB.

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