Manipulating Super-Enhancers to Thwart Drug Resistance in Lymphoma
Clinical studies have demonstrated that although mantle cell and double hit lymphomas driven by BCL2 are sensitive to venetoclax; a selective BCL2 inhibitor, the sensitivity is short lived as inhibitor resistance occurs. Published in Cancer Cell (2019) PMID:31085176, the inter-programmatic team led by Drs. Tao, Koomen, Cleveland (CBE), Silva (CB) and Shain demonstrate that in addition to genetic alterations, drug-resistance occurs as a result of wholesale gene expression changes.
Results derived from a combination of RNAseq, proteomic, genetic studies and pharmacological targeting reveals that BCL2 inhibitor-resistant lymphomas can be re-sensitized by silencing the transcriptional regulating kinase, cyclin dependent kinase 7.