MYC-induced metabolic stress and tumorigenesis

The MYC oncogene is commonly altered across human cancers. Distinct from the normal MYC proto-oncogene, which is under tight transcriptional, translational, and post-translational control, deregulated oncogenic MYC drives imbalanced, non-linear amplification of transcription that results in oncogenic 'stress.' The term 'stress' had been a euphemism for our lack of mechanistic understanding, but synthesis of many studies over the past decade provides a more coherent picture of oncogenic MYC driving metastable cellular states, particularly altered metabolism, that activate and depend on cellular stress response pathways to allow for continued growth and survival. Both deregulated metabolism and these stress response pathways represent vulnerabilities that can be exploited therapeutically.