• Alex Kentsis

  • Jan 09, 2018

Targeting oncogenic transcription factors

Dysregulated control of gene expression is probably one of the essential features of almost every cancer. The causes of this phenomenon vary, but emerging research is converging on the idea that key transcription factors and their regulators may represent optimal targets for cancer therapy. However, identifying the specific molecular determinants of these targets, and achieving their pharmacologic blockade are some of the most difficult problems in experimental therapeutics and oncology.

Now, convergent research from our group and Chris Vakoc indicates that seemingly general transcriptional co-activators can have extraordinarily selective functions in cancer cells, and in the case of AML, in their cooperation with the transcription factor MYB, as summarized in this Twitter thread.

In particular, we have now engineered a prototypical stabilized and cell penetrant peptidomimetic MYB inhibitor, termed MYBMIM, and defined its mechanism and activity against AML. MYBMIM and its inactive analogue TG3 provide a tool for studying MYB-dependent gene control and transcriptional co-activation. In turn, their improved derivatives are expected to offer new therapeutic agents for therapeutic blockade of oncogenic gene expression.