Disrupting proton dynamics and energy metabolism for cancer therapy
- 23 August 2013
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Cancer
- Vol. 13 (9), 611-623
- https://doi.org/10.1038/nrc3579
Abstract
Intense interest in the 'Warburg effect' has been revived by the discovery that hypoxia-inducible factor 1 (HIF1) reprogrammes pyruvate oxidation to lactic acid conversion; lactic acid is the end product of fermentative glycolysis. The most aggressive and invasive cancers, which are often hypoxic, rely on exacerbated glycolysis to meet the increased demand for ATP and biosynthetic precursors and also rely on robust pH-regulating systems to combat the excessive generation of lactic and carbonic acids. In this Review, we present the key pH-regulating systems and synthesize recent advances in strategies that combine the disruption of pH control with bioenergetic mechanisms. We discuss the possibility of exploiting, in rapidly growing tumours, acute cell death by 'metabolic catastrophe'.Keywords
This publication has 166 references indexed in Scilit:
- Macropinocytosis of protein is an amino acid supply route in Ras-transformed cellsNature, 2013
- LKB1 Inactivation Dictates Therapeutic Response of Non-Small Cell Lung Cancer to the Metabolism Drug PhenforminCancer Cell, 2013
- Hypoxia-Inducible Factors in Physiology and MedicineCell, 2012
- Specific inhibition of carbonic anhydrase IX activity enhances the in vivo therapeutic effect of tumor irradiationRadiotherapy and Oncology, 2011
- In vivo pH in metabolic‐defective Ras‐transformed fibroblast tumors: Key role of the monocarboxylate transporter, MCT4, for inducing an alkaline intracellular pHInternational Journal of Cancer, 2011
- Dual inhibition of sodium-mediated proton and calcium efflux triggers non-apoptotic cell death in malignant gliomasBrain Research, 2010
- Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cellsCell Death & Disease, 2010
- Physiological carbon dioxide, bicarbonate, and pH sensingPflügers Archiv - European Journal of Physiology, 2010
- Termination of autophagy and reformation of lysosomes regulated by mTORNature, 2010
- Hypoxia-induced autophagy: cell death or cell survival?Current Opinion in Cell Biology, 2010