What type of study is this?

This is a Animal Study study (also classified as: Pre-Registered Trial).

What question did this study set out to answer?

This research investigates the resistance mechanisms of pediatric brain tumors to ONC201 and paxalisib.

March 14, 2026Neuro-Oncology PediatricsOpen Access

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Single-cell analysis reveals therapeutic resistance mechanisms in pediatric brain tumors, suggesting combination therapies may improve outcomes.

This research investigates the resistance mechanisms of pediatric brain tumors to ONC201 and paxalisib.
Performed single-cell RNA sequencing (scRNA-seq) and ATAC sequencing (scATAC-seq) on a DMG mouse model.
Examined brain tissues from tumor-bearing xenografts treated with optimized paxalisib and metformin.
Analyzed tumor adaptation trajectories and activation of signaling pathways.
Identified distinct tumor adaptation strategies linked to ONC201 and paxalisib treatments.
Confirmed significant activation of the MAPK pathway in ONC201-treated mice.
Observed increased immune cell infiltration but also immunosuppressive characteristics, indicating potential immune escape.

Savary et al. (2025) studied this question.

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Single-cell analysis reveals therapeutic resistance mechanisms in pediatric brain tumors, suggesting combination therapies may improve outcomes.