Metabolic Flexibility: Targeting Mitochondrial Dynamics in Cancer Therapy

1. Bishal Paudel B, Quaranta V. Metabolic plasticity meets gene regulation. Proc Natl Acad Sci U S A [Internet]. 2019 Feb 2 [cited 2024 Feb 29];116(9):3370. Available from: /pmc/articles/PMC6397587/ Bishal Paudel B Quaranta V. Metabolic plasticity meets gene regulation . Proc Natl Acad Sci U S A [Internet]. 2019 Feb 2 [ cited 2024 Feb 29 ]; 116 ( 9 ): 3370 . Available from: /pmc/articles/PMC6397587/ Search in Google Scholar

2. Hirata E, Sahai E. Tumor Microenvironment and Differential Responses to Therapy. Cold Spring Harb Perspect Med [Internet]. 2017 Jul 1 [cited 2024 Feb 29];7(7):1–14. Available from: /pmc/articles/PMC5495051/ Hirata E Sahai E. Tumor Microenvironment and Differential Responses to Therapy . Cold Spring Harb Perspect Med [Internet]. 2017 Jul 1 [ cited 2024 Feb 29 ]; 7 ( 7 ): 1 – 14 . Available from: /pmc/articles/PMC5495051/ Search in Google Scholar

3. Penkert J, Ripperger T, Schieck M, Schlegelberger B, Steinemann D, Illig T. On metabolic reprogramming and tumor biology: A comprehensive survey of metabolism in breast cancer. Oncotarget [Internet]. 2016 Oct 10 [cited 2024 Feb 29];7(41):67626. Available from: /pmc/articles/PMC5341901/ Penkert J Ripperger T Schieck M Schlegelberger B Steinemann D Illig T. On metabolic reprogramming and tumor biology: A comprehensive survey of metabolism in breast cancer . Oncotarget [Internet]. 2016 Oct 10 [ cited 2024 Feb 29 ]; 7 ( 41 ): 67626 . Available from: /pmc/articles/PMC5341901/ Search in Google Scholar

4. Medeiros BC, Fathi AT, DiNardo CD, Pollyea DA, Chan SM, Swords R. Isocitrate dehydrogenase mutations in myeloid malignancies. Leukemia [Internet]. 2017 Feb 1 [cited 2024 Feb 28];31(2): 272–81. Available from: https://pubmed.ncbi.nlm.nih.gov/27721426/ Medeiros BC Fathi AT DiNardo CD Pollyea DA Chan SM Swords R. Isocitrate dehydrogenase mutations in myeloid malignancies . Leukemia [Internet]. 2017 Feb 1 [ cited 2024 Feb 28 ]; 31 ( 2 ): 272 – 81 . Available from: https://pubmed.ncbi.nlm.nih.gov/27721426/ Search in Google Scholar

5. Lycan TW, Pardee TS, Petty WJ, Bonomi M, Alistar A, Lamar ZS, et al. A Phase II Clinical Trial of CPI-613 in Patients with Relapsed or Refractory Small Cell Lung Carcinoma. PLoS One [Internet]. 2016 Oct 1 [cited 2024 Feb 28];11(10). Available from: https://pubmed.ncbi.nlm.nih.gov/27732654/ Lycan TW Pardee TS Petty WJ Bonomi M Alistar A Lamar ZS . A Phase II Clinical Trial of CPI-613 in Patients with Relapsed or Refractory Small Cell Lung Carcinoma . PLoS One [Internet]. 2016 Oct 1 [ cited 2024 Feb 28 ]; 11 ( 10 ) . Available from: https://pubmed.ncbi.nlm.nih.gov/27732654/ Search in Google Scholar

6. Yen K, Travins J, Wang F, David MD, Artin E, Straley K, et al. AG-221, a First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic IDH2 Mutations. Cancer Discov [Internet]. 2017 May 1 [cited 2024 Feb 28];7(5):478–93. Available from: https://pubmed.ncbi.nlm.nih.gov/28193778/ Yen K Travins J Wang F David MD Artin E Straley K . AG-221, a First-in-Class Therapy Targeting Acute Myeloid Leukemia Harboring Oncogenic IDH2 Mutations . Cancer Discov [Internet]. 2017 May 1 [ cited 2024 Feb 28 ]; 7 ( 5 ): 478 – 93 . Available from: https://pubmed.ncbi.nlm.nih.gov/28193778/ Search in Google Scholar

7. Anderson RG, Ghiraldeli LP, Pardee TS. Mitochondria in cancer metabolism, an organelle whose time has come? Biochim Biophys Acta Rev Cancer [Internet]. 2018 Aug 1 [cited 2024 Feb 15]; 1870(1):96–102. Available from: https://pubmed.ncbi.nlm.nih.gov/29807044/ Anderson RG Ghiraldeli LP Pardee TS. Mitochondria in cancer metabolism, an organelle whose time has come? Biochim Biophys Acta Rev Cancer [Internet]. 2018 Aug 1 [ cited 2024 Feb 15 ]; 1870 ( 1 ): 96 – 102 . Available from: https://pubmed.ncbi.nlm.nih.gov/29807044/ Search in Google Scholar

8. Bueno MJ, Ruiz-Sepulveda JL, Quintela-Fandino M. EVOLVING THERAPIES (RM BUKOWSKI, SECTION EDITOR) Mitochondrial Inhibition: a Treatment Strategy in Cancer? 1912 [cited 2024 Feb 15]; Available from: https://doi.org/10.1007/s11912-021-01033-x Bueno MJ Ruiz-Sepulveda JL Quintela-Fandino M. EVOLVING THERAPIES (RM BUKOWSKI, SECTION EDITOR) Mitochondrial Inhibition: a Treatment Strategy in Cancer? 1912 [ cited 2024 Feb 15 ]; Available from: https://doi.org/ 10.1007/s11912-021-01033-x Open DOISearch in Google Scholar

9. Lehúede C, Dupuy F, Rabinovitch R, Jones RG, Siegel PM. Metabolic Plasticity as a Determinant of Tumor Growth and Metastasis. Cancer Res [Internet]. 2016 Sep 15 [cited 2024 Feb 15];76(18): 5201–8. Available from: https://pubmed.ncbi.nlm.nih.gov/27587539/ Lehúede C Dupuy F Rabinovitch R Jones RG Siegel PM. Metabolic Plasticity as a Determinant of Tumor Growth and Metastasis . Cancer Res [Internet]. 2016 Sep 15 [ cited 2024 Feb 15 ]; 76 ( 18 ): 5201 – 8 . Available from: https://pubmed.ncbi.nlm.nih.gov/27587539/ Search in Google Scholar

10. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell [Internet]. 2011 Mar 4 [cited 2024 Feb 15];144(5):646–74. Available from: https://pubmed.ncbi.nlm.nih.gov/21376230/ Hanahan D Weinberg RA. Hallmarks of cancer: the next generation . Cell [Internet]. 2011 Mar 4 [ cited 2024 Feb 15 ]; 144 ( 5 ): 646 – 74 . Available from: https://pubmed.ncbi.nlm.nih.gov/21376230/ Search in Google Scholar

11. Yu L, Chen X, Sun X, Wang L, Chen S. The Glycolytic Switch in Tumors: How Many Players Are Involved? J Cancer [Internet]. 2017 [cited 2024 Feb 15];8(17):3430. Available from: /pmc/articles/PMC5687156/ Yu L Chen X Sun X Wang L Chen S. The Glycolytic Switch in Tumors: How Many Players Are Involved? J Cancer [Internet]. 2017 [ cited 2024 Feb 15 ]; 8 ( 17 ): 3430 . Available from: /pmc/articles/PMC5687156/ Search in Google Scholar

12. Wise DR, Thompson CB. Glutamine addiction: a new therapeutic target in cancer. Trends Biochem Sci [Internet]. 2010 Aug [cited 2024 Feb 28];35(8):427–33. Available from: https://pub-med.ncbi.nlm.nih.gov/20570523/ Wise DR Thompson CB. Glutamine addiction: a new therapeutic target in cancer . Trends Biochem Sci [Internet]. 2010 Aug [ cited 2024 Feb 28 ]; 35 ( 8 ): 427 – 33 . Available from: https://pub-med.ncbi.nlm.nih.gov/20570523/ Search in Google Scholar

13. Cappel DA, Deja S, Duarte JAG, Kucejova B, Iñigo M, Fletcher JA, et al. Pyruvate-Carboxylase-Mediated Anaplerosis Promotes Antioxidant Capacity by Sustaining TCA Cycle and Redox Metabolism in Liver. Cell Metab. 2019 Jun 4;29(6):1291–1305.e8. Cappel DA Deja S Duarte JAG Kucejova B Iñigo M Fletcher JA . Pyruvate-Carboxylase-Mediated Anaplerosis Promotes Antioxidant Capacity by Sustaining TCA Cycle and Redox Metabolism in Liver . Cell Metab . 2019 Jun 4 ; 29 ( 6 ): 1291 – 1305 .e8. Search in Google Scholar

14. Sainero-Alcolado L, Liaño-Pons J, Victoria Ruiz-Pérez M, Arsenian-Henriksson M. Targeting mitochondrial metabolism for precision medicine in cancer. [cited 2024 Feb 15]; Available from: https://doi.org/10.1038/s41418-022-01022-y Sainero-Alcolado L Liaño-Pons J Victoria Ruiz-Pérez M Arsenian-Henriksson M. Targeting mitochondrial metabolism for precision medicine in cancer . [ cited 2024 Feb 15 ]; Available from: https://doi.org/ 10.1038/s41418-022-01022-y Open DOISearch in Google Scholar

15. Rohle D, Popovici-Muller J, Palaskas N, Turcan S, Grommes C, Campos C, et al. An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science [Internet]. 2013 [cited 2024 Feb 28];340(6132):626–30. Available from: https://pubmed.ncbi.nlm.nih.gov/23558169/ Rohle D Popovici-Muller J Palaskas N Turcan S Grommes C Campos C . An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells . Science [Internet]. 2013 [ cited 2024 Feb 28 ]; 340 ( 6132 ): 626 – 30 . Available from: https://pubmed.ncbi.nlm.nih.gov/23558169/ Search in Google Scholar

16. Pardee TS, Lee K, Luddy J, Maturo C, Rodriguez R, Isom S, et al. A phase I study of the first-inclass antimitochondrial metabolism agent, CPI-613, in patients with advanced hematologic malignancies. Clin Cancer Res [Internet]. 2014 Oct 15 [cited 2024 Feb 28];20(20):5255–64. Available from: https://pubmed.ncbi.nlm.nih.gov/25165100/ Pardee TS Lee K Luddy J Maturo C Rodriguez R Isom S . A phase I study of the first-inclass antimitochondrial metabolism agent, CPI-613, in patients with advanced hematologic malignancies . Clin Cancer Res [Internet]. 2014 Oct 15 [ cited 2024 Feb 28 ]; 20 ( 20 ): 5255 – 64 . Available from: https://pubmed.ncbi.nlm.nih.gov/25165100/ Search in Google Scholar

17. Chendong Y, Sudderth J, Tuyen D, Bachoo RG, McDonald JG, DeBerardinis RJ. Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or Akt signaling. Cancer Res [Internet]. 2009 Oct 15 [cited 2024 Feb 16];69(20):7986–93. Available from: https://pubmed.ncbi.nlm.nih.gov/19826036/ Chendong Y Sudderth J Tuyen D Bachoo RG McDonald JG DeBerardinis RJ. Glioblastoma cells require glutamate dehydrogenase to survive impairments of glucose metabolism or Akt signaling . Cancer Res [Internet]. 2009 Oct 15 [ cited 2024 Feb 16 ]; 69 ( 20 ): 7986 – 93 . Available from: https://pubmed.ncbi.nlm.nih.gov/19826036/ Search in Google Scholar

18. Spinelli JB, Yoon H, Ringel AE, Jeanfavre S, Clish CB, Haigis MC. Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass. Science [Internet]. 2017 Nov 17 [cited 2024 Feb 16];358(6365):941–6. Available from: https://pubmed.ncbi.nlm.nih.gov/29025995/ Spinelli JB Yoon H Ringel AE Jeanfavre S Clish CB Haigis MC. Metabolic recycling of ammonia via glutamate dehydrogenase supports breast cancer biomass . Science [Internet]. 2017 Nov 17 [ cited 2024 Feb 16 ]; 358 ( 6365 ): 941 – 6 . Available from: https://pubmed.ncbi.nlm.nih.gov/29025995/ Search in Google Scholar

19. Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, et al. ROS in cancer therapy: the bright side of the moon. Exp Mol Med [Internet]. 2020 Feb 1 [cited 2024 Feb 16];52(2):192–203. Available from: https://pubmed.ncbi.nlm.nih.gov/32060354/ Perillo B Di Donato M Pezone A Di Zazzo E Giovannelli P Galasso G . ROS in cancer therapy: the bright side of the moon . Exp Mol Med [Internet]. 2020 Feb 1 [ cited 2024 Feb 16 ]; 52 ( 2 ): 192 – 203 . Available from: https://pubmed.ncbi.nlm.nih.gov/32060354/ Search in Google Scholar

20. Caro P, Kishan AU, Norberg E, Stanley IA, Chapuy B, Ficarro SB, et al. Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma. Cancer Cell [Internet]. 2012 Oct 16 [cited 2024 Feb 16];22(4):547–60. Available from: https://pubmed.ncbi.nlm.nih.gov/23079663/ Caro P Kishan AU Norberg E Stanley IA Chapuy B Ficarro SB . Metabolic signatures uncover distinct targets in molecular subsets of diffuse large B cell lymphoma . Cancer Cell [Internet]. 2012 Oct 16 [ cited 2024 Feb 16 ]; 22 ( 4 ): 547 – 60 . Available from: https://pubmed.ncbi.nlm.nih.gov/23079663/ Search in Google Scholar

21. Whitaker-Menezes D, Martinez-Outschoorn UE, Flomenberg N, Birbe RC, Witkiewicz AK, Howell A, et al. Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ: visualizing the therapeutic effects of metformin in tumor tissue. Cell Cycle [Internet]. 2011 Dec 1 [cited 2024 Feb 16];10(23):4047–64. Available from: https://pubmed.ncbi.nlm.nih.gov/22134189/ Whitaker-Menezes D Martinez-Outschoorn UE Flomenberg N Birbe RC Witkiewicz AK Howell A . Hyperactivation of oxidative mitochondrial metabolism in epithelial cancer cells in situ: visualizing the therapeutic effects of metformin in tumor tissue . Cell Cycle [Internet]. 2011 Dec 1 [ cited 2024 Feb 16 ]; 10 ( 23 ): 4047 – 64 . Available from: https://pubmed.ncbi.nlm.nih.gov/22134189/ Search in Google Scholar

22. Lonardo E, Cioffi M, Sancho P, Sanchez-Ripoll Y, Trabulo SM, Dorado J, et al. Metformin targets the metabolic achilles heel of human pancreatic cancer stem cells. PLoS One [Internet]. 2013 Oct 18 [cited 2024 Feb 16];8(10). Available from: https://pubmed.ncbi.nlm.nih.gov/24204632/ Lonardo E Cioffi M Sancho P Sanchez-Ripoll Y Trabulo SM Dorado J . Metformin targets the metabolic achilles heel of human pancreatic cancer stem cells . PLoS One [Internet]. 2013 Oct 18 [ cited 2024 Feb 16 ]; 8 ( 10 ) . Available from: https://pubmed.ncbi.nlm.nih.gov/24204632/ Search in Google Scholar

23. Yuan P, Ito K, Perez-Lorenzo R, Del Guzzo C, Lee JH, Shen CH, et al. Phenformin enhances the therapeutic benefit of BRAF(V600E) inhibition in melanoma. Proc Natl Acad Sci U S A [Internet]. 2013 Nov 5 [cited 2024 Feb 16];110(45):18226–31. Available from: https://pubmed.ncbi.nlm.nih.gov/24145418/ Yuan P Ito K Perez-Lorenzo R Del Guzzo C Lee JH Shen CH . Phenformin enhances the therapeutic benefit of BRAF(V600E) inhibition in melanoma . Proc Natl Acad Sci U S A [Internet]. 2013 Nov 5 [ cited 2024 Feb 16 ]; 110 ( 45 ): 18226 – 31 . Available from: https://pubmed.ncbi.nlm.nih.gov/24145418/ Search in Google Scholar

24. Reznik E, Miller ML, Şenbabaoğlu Y, Riaz N, Sarungbam J, Tickoo SK, et al. Mitochondrial DNA copy number variation across human cancers. Elife [Internet]. 2016 Feb 22 [cited 2024 Feb 16];5(FEBRUARY2016). Available from: https://pubmed.ncbi.nlm.nih.gov/26901439/ Reznik E Miller ML Şenbabaoğlu Y Riaz N Sarungbam J Tickoo SK . Mitochondrial DNA copy number variation across human cancers . Elife [Internet]. 2016 Feb 22 [ cited 2024 Feb 16 ]; 5 (FEBRUARY2016). Available from: https://pubmed.ncbi.nlm.nih.gov/26901439/ Search in Google Scholar

25. Zhao Z, Mei Y, Wang Z, He W. The Effect of Oxidative Phosphorylation on Cancer Drug Resistance. Cancers (Basel) [Internet]. 2022 Jan 1 [cited 2024 Feb 28];15(1). Available from: https://pub-med.ncbi.nlm.nih.gov/36612059/ Zhao Z Mei Y Wang Z He W. The Effect of Oxidative Phosphorylation on Cancer Drug Resistance . Cancers (Basel) [Internet]. 2022 Jan 1 [ cited 2024 Feb 28 ]; 15 ( 1 ) . Available from: https://pub-med.ncbi.nlm.nih.gov/36612059/ Search in Google Scholar

26. Spinelli JB, Rosen PC, Sprenger HG, Puszynska AM, Mann JL, Roessler JM, et al. Fumarate is a terminal electron acceptor in the mammalian electron transport chain. Science (1979) [Internet]. 2021 Dec 3 [cited 2024 Feb 13];374(6572):1227–37. Available from: https://www.science.org Spinelli JB Rosen PC Sprenger HG Puszynska AM Mann JL Roessler JM . Fumarate is a terminal electron acceptor in the mammalian electron transport chain . Science (1979) [Internet]. 2021 Dec 3 [ cited 2024 Feb 13 ]; 374 ( 6572 ): 1227 – 37 . Available from: https://www.science.org Search in Google Scholar

27. Navarro P, Bueno MJ, Zagorac I, Mondejar T, Sanchez J, Mourón S, et al. Targeting Tumor Mitochondrial Metabolism Overcomes Resistance to Antiangiogenics. Cell Rep [Internet]. 2016 Jun 21 [cited 2024 Feb 16];15(12):2705–18. Available from: https://pubmed.ncbi.nlm.nih.gov/27292634/ Navarro P Bueno MJ Zagorac I Mondejar T Sanchez J Mourón S . Targeting Tumor Mitochondrial Metabolism Overcomes Resistance to Antiangiogenics . Cell Rep [Internet]. 2016 Jun 21 [ cited 2024 Feb 16 ]; 15 ( 12 ): 2705 – 18 . Available from: https://pubmed.ncbi.nlm.nih.gov/27292634/ Search in Google Scholar

28. Molina JR, Sun Y, Protopopova M, Gera S, Bandi M, Bristow C, et al. An inhibitor of oxidative phosphorylation exploits cancer vulnerability. Nat Med [Internet]. 2018 Jul 1 [cited 2024 Feb 28]; 24(7):1036–46. Available from: https://pubmed.ncbi.nlm.nih.gov/29892070/ Molina JR Sun Y Protopopova M Gera S Bandi M Bristow C . An inhibitor of oxidative phosphorylation exploits cancer vulnerability . Nat Med [Internet]. 2018 Jul 1 [ cited 2024 Feb 28 ]; 24 ( 7 ): 1036 – 46 . Available from: https://pubmed.ncbi.nlm.nih.gov/29892070/ Search in Google Scholar

29. Rohlena J, Dong LF, Ralph SJ, Neuzil J. Anticancer drugs targeting the mitochondrial electron transport chain. Antioxid Redox Signal [Internet]. 2011 Dec 15 [cited 2024 Feb 28];15(12): 2951–74. Available from: https://pubmed.ncbi.nlm.nih.gov/21777145/ Rohlena J Dong LF Ralph SJ Neuzil J. Anticancer drugs targeting the mitochondrial electron transport chain . Antioxid Redox Signal [Internet]. 2011 Dec 15 [ cited 2024 Feb 28 ]; 15 ( 12 ): 2951 – 74 . Available from: https://pubmed.ncbi.nlm.nih.gov/21777145/ Search in Google Scholar

30. Sassi N, Mattarei A, Azzolini M, Szabo’ I, Paradisi C, Zoratti M, et al. Cytotoxicity of mitochondria-targeted resveratrol derivatives: interactions with respiratory chain complexes and ATP synthase. Biochim Biophys Acta [Internet]. 2014 [cited 2024 Feb 28];1837(10):1781–9. Available from: https://pubmed.ncbi.nlm.nih.gov/24997425/ Sassi N Mattarei A Azzolini M Szabo’ I Paradisi C Zoratti M . Cytotoxicity of mitochondria-targeted resveratrol derivatives: interactions with respiratory chain complexes and ATP synthase . Biochim Biophys Acta [Internet]. 2014 [ cited 2024 Feb 28 ]; 1837 ( 10 ): 1781 – 9 . Available from: https://pubmed.ncbi.nlm.nih.gov/24997425/ Search in Google Scholar

31. Baskaran R, Lee J, Yang SG. Clinical development of photodynamic agents and therapeutic applications. Biomater Res [Internet]. 2018 [cited 2024 Feb 28];22. Available from: https://pub-med.ncbi.nlm.nih.gov/30275968/ Baskaran R Lee J Yang SG. Clinical development of photodynamic agents and therapeutic applications . Biomater Res [Internet]. 2018 [ cited 2024 Feb 28 ]; 22 . Available from: https://pub-med.ncbi.nlm.nih.gov/30275968/ Search in Google Scholar

32. Shrestha R, Johnson E, Byrne FL. Exploring the therapeutic potential of mitochondrial uncouplers in cancer. Mol Metab [Internet]. 2021 Sep 1 [cited 2024 Feb 28];51. Available from: https://pubmed.ncbi.nlm.nih.gov/33781939/ Shrestha R Johnson E Byrne FL. Exploring the therapeutic potential of mitochondrial uncouplers in cancer . Mol Metab [Internet]. 2021 Sep 1 [ cited 2024 Feb 28 ]; 51 . Available from: https://pubmed.ncbi.nlm.nih.gov/33781939/ Search in Google Scholar