Thomas Seyfried and colleagues revisit Otto Warburg’s theory that cancer arises from impaired mitochondrial oxidative phosphorylation (OxPhos), leading to increased reliance on fermentation for energy production.

Seyfried argues that modern evidence supports Warburg’s central idea, highlighting that neither oxygen consumption nor lactate production accurately reflect ATP generation in cancer cells, and that mitochondrial dysfunction plays a pivotal role in cancer development.

“Warburg’s original hypothesis can now be linked to a more complete understanding of how OxPhos insufficiency underlies dysregulated cancer cell growth.”