In an extensive screening study utilizing genome-scale, pooled lentiviral open reading frame (ORF), and CRISPR knockout rescue techniques, the upregulation of RTKs, activation of PI3K signaling pathway, and a global enhancer remodeling were generally observed in various in vitro neuroblastoma cell models exhibiting acquired resistance to BET inhibitors [168]. This evidence concerns the gene DNER and neuroblastoma.