The Myc oncogene features prominently in human cancers, being overexpressed or activated in more than 70% of malignancies (1). It is a basic helix-loop-helix (bHLH) transcription factor that lies at the crossroads of many growth-promoting signal transduction and bioenergetic pathways (2). Genetic studies in animal models have revealed that suppression of Myc activation leads to rapid tumor shrinkage caused by inhibition of cell proliferation, induction of senescence, and apoptosis, as well as remodeling of the tumor microenvironment (3). This phenomenon, coined “oncogene addiction,” has been demonstrated to be a feature of tumors even when MYC is not the initiating oncogenic event, thus rendering MYC a coveted therapeutic target (4).
Insights into the regulation of MYC expression and function have shed light on the development of novel therapies. BET bromodomain-containing proteins were found to be potent regulators of MYC expression through association with active enhancer elements. This has led to the development of the BET bromodomain inhibitor, JQ1, as a powerful therapeutic in murine models of hematological malignancies (5,6). Unfortunately, JQ1 exhibits limited effect in other cancer types, possibly because of lineage-dependent differences in the epigenetic landscape or different mechanisms that regulate MYC expression independent of enhance
