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June 26, 2026Neuro-Oncology PediatricsOpen Access

ID #771 Inhibition of MCL-1-mediated anti-apoptotic signalling as a potential therapeutic strategy for paediatric high-grade gliomas

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Authors

DLDavid LawrenceJCJacob Wright CurnowCUCaitlin Ung

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Overview

Randomized trial evaluates MCL-1 inhibitors to enhance survival in glioma patients, suggesting new therapeutic avenues.

Key Points

  • This research aims to explore the role of MCL-1 inhibitors in overcoming resistance in high-grade gliomas in pediatric patients.
  • Evaluated MCL-1 inhibitors (S63845, MIK665, BRD-810) and BCL-2 inhibitor venetoclax in glioma cultures.
  • Performed protein analysis using Western blot and gene expression analysis via RT-qPCR to confirm MCL-1 upregulation.
  • Assessed in vivo effects of MCL-1 inhibition on survival in DMG and HGG models.
  • MIK665 was the most effective in inducing apoptosis in HGG and DMG cells without toxicity to healthy cells.
  • MCL-1 inhibition (S63845) significantly increased survival rates in two DMG models and one HGG model.
  • Combination of MIK665 with CBL-037 exhibited strong synergistic effects in DMG cells, enhancing therapeutic efficacy.

Cite This Study

Lawrence et al. (2026) studied this question.

synapsesocial.com/papers/6a3e1a65030ad1a9b3092db5https://doi.org/10.1093/neuped/wuag026.326
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