Hidden cellular vulnerability to lipids

The prevailing paradigm holds that tumour cells exposed to an acidic environment adapt their metabolism by shifting from sugar to fatty acid utilisation.  Olivier Feron’s team (WEL Research Institute – UCLouvain) has challenged this view by revealing that it is the microenvironment, rather than an intrinsic metabolic shift, that dictates fatty acid preference. 

The researchers demonstrated that, in acidic conditions, fatty acids became protonated and were more readily taken up by cells. The resulting overload of very long-chain fatty acids created a metabolic burden, rendering cancer cells highly dependent on peroxisomes for detoxification. Disrupting peroxisomal function selectively eliminated cancer cells in such acidic environments. This vulnerability has been confirmed in patient-derived tumour organoids and in experiments using human sera.  Importantly, the same acid-driven fatty acid uptake was observed in endothelial and cardiac cells, opening up the door to novel therapeutic opportunities not only in oncology but also in cardiovascular diseases.

Reference : Ibanez et al, Acidosis forces fatty acid uptake and metabolism in cancer cells regardless of genotype, Adv Sci (2025) e05436

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