Metabolic Regulation in Myc-Driven Cancers

The Myc family of transcription factors, notably c-Myc and its paralogue N-Myc, orchestrates a comprehensive reprogramming of cellular metabolism to support rapid proliferation and survival in malignant cells. By directly upregulating genes involved in glucose uptake and glycolysis, Myc enhances lactate production and diverts glycolytic intermediates into biosynthetic pathways. Concurrently, Myc promotes glutaminolysis by inducing expression of glutamine transporters and enzymes that funnel glutamine into the tricarboxylic acid cycle, supplying carbon and nitrogen for nucleotide and amino acid synthesis. In parallel, Myc drives mitochondrial biogenesis and function, balancing oxidative phosphorylation with the need for anabolic precursors such as acetyl-CoA for lipid synthesis and histone acetylation. Lipid metabolic programmes are also reshaped under Myc control, with fatty acid synthesis and β-oxidation pathways adjusted to meet membrane biogenesis and energy demands. Beyond bioenergetics, Myc-induced redox modulation maintains cellular homeostasis under oxidative stress, creating unique vulnerabilities. This metabolic remodelling underpins the Warburg effect and exposes dependencies that may be exploited therapeutically. Integrating these interwoven programmes, Myc-driven cancers display extraordinary metabolic plasticity, which facilitates adaptation to varying nutrient and oxygen availability, promotes tumour progression and influences response to targeted therapies.

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Metabolic Regulation in Myc-Driven Cancers publication trend

The graph below shows the total number of articles in metabolic regulation in myc-driven cancers across all publications each year (not limited to Nature Index journals).

Technical terms

Myc: A family of oncogenic transcription factors (c-Myc, N-Myc) that regulate genes controlling growth, proliferation and metabolism.

Glycolysis: The enzymatic breakdown of glucose to pyruvate, generating ATP and biosynthetic intermediates.

Glutaminolysis: The catabolism of glutamine to feed the tricarboxylic acid cycle and support nucleotide and amino acid synthesis.

Oxidative phosphorylation (OXPHOS): The mitochondrial process that generates ATP via electron transport and proton gradient across the inner membrane.

Fatty acid β-oxidation: The sequential removal of two-carbon units from fatty acids to produce acetyl-CoA and reducing equivalents.

Tricarboxylic acid (TCA) cycle: A central mitochondrial pathway that oxidises acetyl-CoA to CO₂, yielding ATP precursors and biosynthetic substrates.

Warburg effect: The tendency of cancer cells to prefer glycolysis over OXPHOS for energy generation, even under normoxic conditions.

References

1. Lipid Metabolic Reprogramming in Embryonal Neoplasms with MYCN Amplification. Cancers (2023).
2. Regulation of cancer cell metabolism: oncogenic MYC in the driver’s seat. Signal Transduction and Targeted Therapy (2020).
3. The Role for Myc in Coordinating Glycolysis, Oxidative Phosphorylation, Glutaminolysis, and Fatty Acid Metabolism in Normal and Neoplastic Tissues. Frontiers in Endocrinology (2018).
4. MYCN drives glutaminolysis in neuroblastoma and confers sensitivity to an ROS augmenting agent. Cell Death & Disease (2018).