From Tissue Specificity to Systemic Cues: Shaping MYC‑Driven Tumor Metabolism

The proto-oncogene MYC acts as a master regulator of diverse metabolic programs that fuel tumor initiation and progression, but the exact programs it activates depend heavily on context, tissue type, accompanying mutations, and the tumor microenvironment (TME). Furthermore, extrinsic influences, including diet and systemic metabolism, interact with MYC to reshape tumor and stromal cell metabolism, revealing a multifaceted metabolic landscape governed by MYC. This review focuses on MYC-driven in vivo metabolic addictions and discusses tissue-specific programs, TME interactions, and systemic influences to illustrate how MYC-driven metabolic reprogramming creates context-dependent vulnerabilities. These insights may uncover actionable targets and guide precision therapeutic strategies for MYC-driven cancers.