Pan-cyclin-dependent kinase inhibition is a potential treatment for adenoid cystic carcinoma that downregulates the MYB::NFIB fusion and induces tumor regression

Adenoid cystic carcinoma (ACC) is a MYB-driven, aggressive glandular cancer with a poor long-term prognosis that is resistant to systemic therapies. Therefore, there is an urgent need to develop novel therapeutic strategies for these patients. An in vitro small-molecule inhibitor screen identified sensitivity of cultured ACC cells to pan-CDK inhibitors. We here used RNA-seq analysis to investigate the cell biological and molecular effects of treatment with the pan-CDK inhibitor dinaciclib in ACC cells from two different cases. Our results show that dinaciclib treatment led to a downregulation of genes involved in cell cycle progression, DNA replication, and DNA repair. Upregulated genes affected programmed cell death and included genes involved in proteolysis and autophagy. ACC MYB signature genes were significantly downregulated in dinaciclib-treated ACC cells, indicating that dinaciclib perturbs MYB-driven gene expression. Overall design: Cultured ACCX11 and ACCX67 cells treated with 25 nM dinaciclib or DMSO (vehicle control) for 24 h.