Synergistic anti-tumor effect of combining selective CDK7 and BRD4 inhibition in MYCN-amplified neuroblastoma

Cyclin-dependent kinases (CDKs) that have critical roles in RNA polymerase II (Pol II)-mediated gene transcription are emerging as therapeutic targets in cancer. We have previously shown that THZ1, a covalent inhibitor of CDKs7/12/13, leads to cytotoxicity in MYCN-amplified neuroblastoma through the downregulation of super-enhancer-associated transcriptional upregulation. We sought to dissect the mechanisms of cytotoxicity in NB cells and to identify additional targets that could be inhibited together with CDK7 in combination therapy. RNA-Seq in human neuroblastoma cells treated with CDK7 inhibitor (YKL-5-124), BRD4 inhibitor (JQ1) or both. DMSO treated cells were used as control.