What Cancer Cells Use as Energy
Cancer cells primarily use glucose as their main energy source, converting it to lactate through aerobic glycolysis (the Warburg effect) even when oxygen is present, rather than relying on the more efficient mitochondrial oxidative phosphorylation used by normal cells. 1, 2
Primary Energy Substrate: Glucose
Cancer cells exhibit dramatically increased glucose consumption compared to normal cells, with typical uptake rates ranging from 100-400 nmol/10⁶ cells/h and lactate secretion rates of 200-700 nmol/10⁶ cells/h. 1 This metabolic shift is driven by neoplastic transformation that upregulates glucose transporters (particularly GLUT1) and glycolytic enzymes (particularly hexokinase). 2
The reliance on glycolysis over oxidative phosphorylation occurs despite oxygen availability—this is the defining feature of the Warburg effect. 2, 3 While glycolysis produces less ATP per glucose molecule than oxidative phosphorylation, cancer cells compensate by dramatically increasing their glucose uptake rate. 4
Secondary Energy Source: Glutamine
Glutamine serves as the second most highly consumed carbon substrate by many cancer cells after glucose. 5 When tumor hypoxia develops, tumor metabolism shifts to rely more heavily on glycolysis and less on oxidative phosphorylation. 6
Metabolic Rationale for This Energy Strategy
This metabolic adaptation allows cancer cells to extract not just energy (ATP), but also cellular building blocks and anabolic precursors needed for rapid proliferation. 1, 2 The metabolic pathways involved include:
- Glycolysis for ATP production and biosynthetic intermediates 6
- Pentose phosphate pathway (PPP) branching from glycolysis 6
- TCA cycle with altered flux patterns 6
- Reductive carboxylation of glutamine for lipid synthesis 6
Cancer cells require approximately 315 nmol/10⁶ cells/h of ATP and 55 nmol/10⁶ cells/h of NADPH for cell growth, with specific biosynthetic precursor fluxes including acetyl-CoA to fatty acids (28 nmol/10⁶ cells/h) and ribose-5-phosphate to nucleotides (3 nmol/10⁶ cells/h). 6
Clinical Implications
This glucose dependency forms the biological basis for FDG-PET scanning in oncology, as the increased glucose uptake by cancer cells allows for tumor detection and staging. 2 However, glucose accumulation is not entirely specific to malignant tumors and can occur in benign tumors and inflammatory diseases such as sarcoidosis and granulomatosis. 2
Important Caveats
The metabolic profile of cancer cells shows considerable plasticity and heterogeneity. 7 Tumor hypoxia—which occurs when rapidly growing tumors outpace their blood supply—further alters metabolism and is associated with enhanced tumor growth, malignant progression, and resistance to anticancer therapy. 6 This metabolic flexibility represents both a therapeutic target and a challenge, as cancer cells can activate compensatory metabolic routes when specific pathways are inhibited. 3