Combining inhibitors of Brd4 and cyclin-dependent kinase can decrease tumor growth in neuroblastoma with MYCN amplification.

ABSTRACT:

Introduction

High-risk neuroblastoma is a deadly disease; poor prognosticators are MYCN-amplification and TERT-overexpression. We hypothesized that Gene Set Enrichment Analysis (GSEA) could identify pathways associated with MYCN-amplification and that inhibition of these pathways could decrease tumor growth.

Methods

We analyzed the Neuroblastoma-Kocak dataset (GSE45547, n = 649) and identified pathways associated with MYCN-amplification. Inhibitors were selected from upregulated gene sets for in vitro cytotoxicity testing using ST16-patient-derived primary neuroblastoma cells and in vivo testing using orthotopic ST16-patient-derived xenografts (PDX) in mice. Tumor volume was measured with ultrasound and tumor sections examined after H&E staining.

Results

GSEA identifi

SUBMITTER: Wood L 

PROVIDER: S-EPMC8225564 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature