Resistance Is Futile: Targeting Mitochondrial Energetics and Metabolism to Overcome Drug Resistance in Cancer Treatment  Claudie Bosc, Mary A. Selak, Jean-Emmanuel Sarry  Cell Metabolism  Volume 26, Issue 5, Pages 705-707 (November 2017) DOI: 10.1016/j.cmet.2017.10.013 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Mitochondrial Oxidative Phosphorylation Drives Resistance to Chemotherapy in Leukemia and Cancer (A) Overview of a cancer translational research methodology based on PDX models that mimic the patient disease and treatment response. (B) Mitochondrial mass, mitochondrial membrane potential, mitochondrial ATP production, mitochondrial oxygen consumption rates, Krebs cycle intermediates, mitochondrial fatty acid β-oxidation, and gene signature, all consistent with a high mitochondrial oxidative phosphorylation (OXPHOS) status, are increased or enriched in residual cells after chemotherapy in cancer and AML. (C) Some types of chemotherapy induce resistance via metabolic reprogramming toward OXPHOS. Targeting high OXPHOS activity with mitochondrial inhibitors leads to an energetic and metabolic shift toward glycolysis and sensitizes cells to chemotherapy. (D) Schematic diagram of the metabolic state of cancer cells. In responders, cancer cells predominately utilize glycolysis to produce cytosolic ATP and lactate, while non-responders rely preferentially on OXPHOS to produce energy. The in vivo protective and nutrient-supportive local niche can sustain chemoresistance by providing oxidizable substrates to fuel mitochondrial OXPHOS of cancer cells. Cell Metabolism 2017 26, 705-707DOI: (10.1016/j.cmet.2017.10.013) Copyright © 2017 Elsevier Inc. Terms and Conditions