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Updated: May 13, 2026

Zebrafish Model of Neuroblastoma Metastasis
05:20

Zebrafish Model of Neuroblastoma Metastasis

Published on: March 14, 2021

Targeting MYCN in neuroblastoma by BET bromodomain inhibition

Alexandre Puissant1, Stacey M Frumm, Gabriela Alexe

  • 1Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA.

Cancer Discovery
|February 23, 2013
PubMed

Insights

Bromodomain inhibitors show promise for cancer therapy. Researchers found MYCN amplification predicts sensitivity to these drugs, particularly in neuroblastoma, suggesting a new biomarker for treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Bromodomain inhibition is a potential cancer therapy, especially for blood cancers.
  • Genomic biomarkers for guiding bromodomain inhibitor treatment are currently lacking.
  • BET bromodomain inhibitors target specific protein interactions involved in gene regulation.

Purpose of the Study:

  • To identify genomic biomarkers predicting sensitivity to bromodomain inhibitors.
  • To investigate the role of MYCN amplification in response to bromodomain inhibition.
  • To evaluate the therapeutic potential of BET bromodomain inhibitors in neuroblastoma.

Main Methods:

  • Conducted a cell-based screen of genetically defined cancer cell lines with a BET bromodomain inhibitor.
  • Integrated genetic features with chemosensitivity data to identify correlations.
  • Performed genome-wide expression analysis and functional assays in neuroblastoma models.
  • Evaluated BET inhibition in in vivo neuroblastoma models.

Main Results:

  • Identified a strong correlation between MYCN amplification and sensitivity to bromodomain inhibition.
  • Demonstrated that BET bromodomain inhibition downregulates the MYCN transcriptional program and suppresses MYCN transcription.
  • Showed that bromodomain inhibition impairs neuroblastoma growth and induces apoptosis.
  • Confirmed BRD4 knockdown phenocopies these effects, establishing BET bromodomains as MYCN regulators.
  • BET inhibition significantly improved survival in preclinical neuroblastoma models.

Conclusions:

  • MYCN amplification serves as a predictive biomarker for bromodomain inhibitor sensitivity in cancer.
  • BET bromodomain inhibitors represent a promising therapeutic strategy for neuroblastoma.
  • Targeting BET bromodomains offers a viable approach for treating MYCN-amplified cancers.

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