MYC is a transcription factor, which not only directly modulates multiple aspects of transcription and co-transcriptional processing (e.g. RNA-Polymerase II initiation, elongation, and mRNA capping), but also indirectly influences several steps of RNA metabolism, including both constitutive and alternative splicing, mRNA stability, and translation efficiency. As MYC is an oncoprotein whose expression is deregulated in multiple human cancers, identifying its critical downstream activities in tumors is of key importance for designing effective therapeutic strategies. With this knowledge and recent technological advances, we now have multiple angles to reach the goal of targeting MYC in tumors, ranging from the direct reduction of MYC levels, to the dampening of selected house-keeping functions in MYC-overexpressing cells, to more targeted approaches based on MYC-induced secondary effects.
Cancer cells express high levels of MYC:MAX, and Myc/MYC abundance can be directly targeted for cancer therapy (1). Additionally, MYC-overexpressing cells have an increased dependence on core MYC-regulated functions, compared to normal cells. These functions therefore present potential points of synthetic lethality that may be exploited in anti-cancer therapies (2).