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Updated: Dec 15, 2025

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Proteasome inhibition as a therapeutic approach in atypical teratoid/rhabdoid tumors

Andrew Morin1,2, Caroline Soane1, Angela Pierce1,2

  • 1Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado.

Neuro-Oncology Advances
|July 10, 2020
PubMed
Abstract

Insights

Marizomib (MRZ), a proteasome inhibitor, shows significant efficacy against atypical teratoid/rhabdoid tumors (AT/RT) in preclinical models. This drug effectively inhibits AT/RT cell growth and extends survival, indicating its potential for clinical trials.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and aggressive brain tumor with poor prognosis.
  • Current treatment options for AT/RT are limited, highlighting the need for novel therapeutic strategies.
  • Proteasome inhibitors have emerged as a promising class of drugs for cancer treatment.

Purpose of the Study:

  • To identify and characterize a pre-approved targeted therapy for AT/RT with potential for clinical trials.
  • To evaluate the efficacy of proteasome inhibitors in preclinical AT/RT models.

Main Methods:

  • A drug screen of 134 FDA-approved drugs was conducted using three AT/RT cell lines.
  • In vitro studies utilized six cell lines and patient-derived cultures to assess drug interactions.
  • In vivo efficacy was evaluated using patient-derived xenografts in an intracranial murine model.

Main Results:

  • Bortezomib (BTZ) and carfilzomib (CFZ) demonstrated potent in vitro inhibition of AT/RT cell growth.
  • Marizomib (MRZ), a proteasome inhibitor that crosses the blood-brain barrier (BBB), strongly inhibited AT/RT proteasomes and induced rapid cell death.
  • MRZ significantly extended survival in an intracranial mouse model of AT/RT.

Conclusions:

  • MRZ exhibits strong in vitro and in vivo efficacy against AT/RT, demonstrating direct translational potential.
  • MRZ's ability to cross the BBB makes it a promising candidate for treating brain tumors like AT/RT.
  • MRZ is currently in Phase II clinical trials for adult high-grade glioma, suggesting its clinical relevance.
Keywords:
drug screenmarizomibproteasomerhabdoid tumors

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