In tumors, the concentration of glucose and other nutrients is generally lower than in healthy tissues. Thus, in order to survive in a hostile environment, cancer cells activate metabolic pathways that are normally absent in healthy cells. The nature of these pathways, however, remains largely elusive.
David M. Sabatini, Whitehead Institute for Biomedical Research, Cambridge, MA, USA, and co-workers discovered that the mitochondrial oxidative phosphorylation (OXPHOS), a process whereby nutrients are oxidized to form ATP, renders cancer cells able to proliferate in low glucose concentrations. Tumor cells obtained from patients bearing a defective OXPHOS only poorly grew in a low-glucose environment. Furthermore, the lack of a functional OXPHOS rendered these cancer cells sensitive to the action of biguanides, a class of antidiabetic drugs.
Biguanides may, thus, constitute an important therapeutic strategy for patients bearing genetic defects in OXPHOS.
- Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides,
Kıvanç Birsoy, Richard Possemato, Franziska K. Lorbeer, Erol C. Bayraktar, Prathapan Thiru, Burcu Yucel, Tim Wang, Walter W. Chen, Clary B. Clish, David M. Sabatini,
Nature 2014, 508, 108–112.