Koppenol WH, Bounds PL, Dang CV. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011;11(5):325–37.
Article
CAS
PubMed
Google Scholar
Porporato PE, Filigheddu N, Pedro JMB, Kroemer G, Galluzzi L. Mitochondrial metabolism and cancer. Cell Res. 2018;28(3):265–80.
Article
CAS
PubMed
Google Scholar
Ashton TM, McKenna WG, Kunz-Schughart LA, Higgins GS. Oxidative Phosphorylation as an Emerging Target in Cancer Therapy. Clin Cancer Res. 2018;24(11):2482–90.
Article
CAS
PubMed
Google Scholar
Ghosh P, Vidal C, Dey S, Zhang L. Mitochondria Targeting as an Effective Strategy for Cancer Therapy. Int J Mol Sci. 2020;21(9):336.
Article
CAS
Google Scholar
Monk BJ, Kauderer JT, Moxley KM, Bonebrake AJ, Dewdney SB, Secord AA, et al. A phase II evaluation of elesclomol sodium and weekly paclitaxel in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube or primary peritoneal cancer: An NRG oncology/gynecologic oncology group study. Gynecol Oncol. 2018;151(3):422–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Nagai M, Vo NH, Shin Ogawa L, Chimmanamada D, Inoue T, Chu J, et al. The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells. Free Radical Biol Med. 2012;52(10):2142–50.
Article
CAS
Google Scholar
Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins. Science (New York, NY). 2022;375(6586):1254–61.
Article
CAS
Google Scholar
Chen S, Sun L, Koya K, Tatsuta N, Xia Z, Korbut T, et al. Syntheses and antitumor activities of N’1, N’3-dialkyl-N’1, N’3-di-(alkylcarbonothioyl) malonohydrazide: the discovery of elesclomol. Bioorg Med Chem Lett. 2013;23(18):5070–6.
Article
CAS
PubMed
Google Scholar
Berkenblit A, Eder JP Jr, Ryan DP, Seiden MV, Tatsuta N, Sherman ML, et al. Phase I clinical trial of STA-4783 in combination with paclitaxel in patients with refractory solid tumors. Clin Cancer Res. 2007;13(2 Pt 1):584–90.
Article
CAS
PubMed
Google Scholar
Hedley D, Shamas-Din A, Chow S, Sanfelice D, Schuh AC, Brandwein JM, et al. A phase I study of elesclomol sodium in patients with acute myeloid leukemia. Leuk Lymphoma. 2016;57(10):2437–40.
Article
PubMed
Google Scholar
O’Day S, Gonzalez R, Lawson D, Weber R, Hutchins L, Anderson C, et al. Phase II, randomized, controlled, double-blinded trial of weekly elesclomol plus paclitaxel versus paclitaxel alone for stage IV metastatic melanoma. J Clin Oncol. 2009;27(32):5452–8.
Article
CAS
PubMed
Google Scholar
O’Day SJ, Eggermont AM, Chiarion-Sileni V, Kefford R, Grob JJ, Mortier L, et al. Final results of phase III SYMMETRY study: randomized, double-blind trial of elesclomol plus paclitaxel versus paclitaxel alone as treatment for chemotherapy-naive patients with advanced melanoma. J Clin Oncol. 2013;31(9):1211–8.
Article
CAS
PubMed
Google Scholar
Koukourakis MI, Giatromanolaki A, Sivridis E, Bougioukas G, Didilis V, Gatter KC, et al. Lactate dehydrogenase-5 (LDH-5) overexpression in non-small-cell lung cancer tissues is linked to tumour hypoxia, angiogenic factor production and poor prognosis. Br J Cancer. 2003;89(5):877–85.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gohil VM. Repurposing elesclomol, an investigational drug for the treatment of copper metabolism disorders. Expert Opin Investig Drugs. 2021;30(1):1–4.
Article
CAS
PubMed
Google Scholar
Guthrie LM, Soma S, Yuan S, Silva A, Zulkifli M, Snavely TC, et al. Elesclomol alleviates Menkes pathology and mortality by escorting Cu to cuproenzymes in mice. Science (New York, NY). 2020;368(6491):620–5.
Article
CAS
Google Scholar
Kirshner JR, He S, Balasubramanyam V, Kepros J, Yang CY, Zhang M, et al. Elesclomol induces cancer cell apoptosis through oxidative stress. Mol Cancer Ther. 2008;7(8):2319–27.
Article
CAS
PubMed
Google Scholar
Wangpaichitr M, Wu C, You M, Maher JC, Dinh V, Feun LG, et al. N’, N’-Dimethyl-N’, N’-bis(phenylcarbonothioyl) Propanedihydrazide (Elesclomol) Selectively Kills Cisplatin Resistant Lung Cancer Cells through Reactive Oxygen Species (ROS). Cancers. 2009;1(1):23–38.
Article
CAS
PubMed
PubMed Central
Google Scholar
Barbi de Moura M, Vincent G, Fayewicz SL, Bateman NW, Hood BL, Sun M, et al. Mitochondrial respiration–an important therapeutic target in melanoma. PloS One. 2012;7(8):e40690.
Article
PubMed
PubMed Central
CAS
Google Scholar
Blackman RK, Cheung-Ong K, Gebbia M, Proia DA, He S, Kepros J, et al. Mitochondrial electron transport is the cellular target of the oncology drug elesclomol. PLoS One. 2012;7(1):e29798.
Article
CAS
PubMed
PubMed Central
Google Scholar
Corazao-Rozas P, Guerreschi P, Jendoubi M, André F, Jonneaux A, Scalbert C, et al. Mitochondrial oxidative stress is the Achille’s heel of melanoma cells resistant to Braf-mutant inhibitor. Oncotarget. 2013;4(11):1986–98.
Article
PubMed
PubMed Central
Google Scholar
Kwan SY, Cheng X, Tsang YT, Choi JS, Kwan SY, Izaguirre DI, et al. Loss of ARID1A expression leads to sensitivity to ROS-inducing agent elesclomol in gynecologic cancer cells. Oncotarget. 2016;7(35):56933–43.
Article
PubMed
PubMed Central
Google Scholar
Lee JH, Cho YS, Jung KH, Park JW, Lee KH. Genipin enhances the antitumor effect of elesclomol in A549 lung cancer cells by blocking uncoupling protein-2 and stimulating reactive oxygen species production. Oncol Lett. 2020;20(6):374.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wong HN, Lewies A, Haigh M, Viljoen JM, Wentzel JF, Haynes RK, et al. Anti-Melanoma Activities of Artemisone and Prenylated Amino-Artemisinins in Combination With Known Anticancer Drugs. Front Pharmacol. 2020;11:558894.
Article
CAS
PubMed
PubMed Central
Google Scholar
Buccarelli M, D’Alessandris QG, Matarrese P, Mollinari C, Signore M, Cappannini A, et al. Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth. J Exp Clin Cancer Res. 2021;40(1):228.
Article
CAS
PubMed
PubMed Central
Google Scholar
Kluza J, Corazao-Rozas P, Touil Y, Jendoubi M, Maire C, Guerreschi P, et al. Inactivation of the HIF-1α/PDK3 signaling axis drives melanoma toward mitochondrial oxidative metabolism and potentiates the therapeutic activity of pro-oxidants. Can Res. 2012;72(19):5035–47.
Article
CAS
Google Scholar
Wangpaichitr M, Sullivan EJ, Theodoropoulos G, Wu C, You M, Feun LG, et al. The relationship of thioredoxin-1 and cisplatin resistance: its impact on ROS and oxidative metabolism in lung cancer cells. Mol Cancer Ther. 2012;11(3):604–15.
Article
CAS
PubMed
PubMed Central
Google Scholar
Cierlitza M, Chauvistré H, Bogeski I, Zhang X, Hauschild A, Herlyn M, et al. Mitochondrial oxidative stress as a novel therapeutic target to overcome intrinsic drug resistance in melanoma cell subpopulations. Exp Dermatol. 2015;24(2):155–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tsvetkov P, Detappe A, Cai K, Keys HR, Brune Z, Ying W, et al. Mitochondrial metabolism promotes adaptation to proteotoxic stress. Nat Chem Biol. 2019;15(7):681–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Harrington BS, Ozaki MK, Caminear MW, Hernandez LF, Jordan E, Kalinowski NJ, et al. Drugs Targeting Tumor-Initiating Cells Prolong Survival in a Post-Surgery, Post-Chemotherapy Ovarian Cancer Relapse Model. Cancers. 2020;12(6):1645.
Article
CAS
PubMed Central
Google Scholar
Meng E, Long B, Sullivan P, McClellan S, Finan MA, Reed E, et al. CD44+/CD24- ovarian cancer cells demonstrate cancer stem cell properties and correlate to survival. Clin Exp Metas. 2012;29(8):939–48.
Article
CAS
Google Scholar
House CD, Hernandez L, Annunziata CM. In vitro enrichment of ovarian cancer tumor-initiating cells. J Vis Exp. 2015;(96):52446.
Kim B, Jung JW, Jung J, Han Y, Suh DH, Kim HS, et al. PGC1α induced by reactive oxygen species contributes to chemoresistance of ovarian cancer cells. Oncotarget. 2017;8(36):60299–311.
Article
PubMed
PubMed Central
Google Scholar
House CD, Jordan E, Hernandez L, Ozaki M, James JM, Kim M, et al. NFκB Promotes Ovarian Tumorigenesis via Classical Pathways That Support Proliferative Cancer Cells and Alternative Pathways That Support ALDH(+) Cancer Stem-like Cells. Can Res. 2017;77(24):6927–40.
Article
CAS
Google Scholar
Sighel D, Notarangelo M, Aibara S, Re A, Ricci G, Guida M, et al. Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth. Cell Rep. 2021;35(4):109024.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lv P, Man S, Xie L, Ma L, Gao W. Pathogenesis and therapeutic strategy in platinum resistance lung cancer. Biochim Biophys Acta. 2021;1876(1):188577.
CAS
Google Scholar
Rossi A, Roberto M, Panebianco M, Botticelli A, Mazzuca F, Marchetti P. Drug resistance of BRAF-mutant melanoma: Review of up-to-date mechanisms of action and promising targeted agents. Eur J Pharmacol. 2019;862:172621.
Article
CAS
PubMed
Google Scholar
Bristot IJ, Kehl Dias C, Chapola H, Parsons RB, Klamt F. Metabolic rewiring in melanoma drug-resistant cells. Crit Rev Oncol Hematol. 2020;153:102995.
Article
PubMed
Google Scholar
Cruz-Bermúdez A, Laza-Briviesca R, Vicente-Blanco RJ, García-Grande A, Coronado MJ, Laine-Menéndez S, et al. Cisplatin resistance involves a metabolic reprogramming through ROS and PGC-1α in NSCLC which can be overcome by OXPHOS inhibition. Free Radical Biol Med. 2019;135:167–81.
Article
CAS
Google Scholar
Roesch A, Fukunaga-Kalabis M, Schmidt EC, Zabierowski SE, Brafford PA, Vultur A, et al. A temporarily distinct subpopulation of slow-cycling melanoma cells is required for continuous tumor growth. Cell. 2010;141(4):583–94.
Article
CAS
PubMed
PubMed Central
Google Scholar
Roesch A, Vultur A, Bogeski I, Wang H, Zimmermann KM, Speicher D, et al. Overcoming intrinsic multidrug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1B(high) cells. Cancer Cell. 2013;23(6):811–25.
Article
CAS
PubMed
Google Scholar
Livingstone E, Swann S, Lilla C, Schadendorf D, Roesch A. Combining BRAF(V) (600E) inhibition with modulators of the mitochondrial bioenergy metabolism to overcome drug resistance in metastatic melanoma. Exp Dermatol. 2015;24(9):709–10.
Article
PubMed
Google Scholar
Adams J, Palombella VJ, Sausville EA, Johnson J, Destree A, Lazarus DD, et al. Proteasome inhibitors: a novel class of potent and effective antitumor agents. Can Res. 1999;59(11):2615–22.
CAS
Google Scholar
Orlowski RZ, Kuhn DJ. Proteasome inhibitors in cancer therapy: lessons from the first decade. Clin Cancer Res. 2008;14(6):1649–57.
Article
CAS
PubMed
Google Scholar
Marroquin LD, Hynes J, Dykens JA, Jamieson JD, Will Y. Circumventing the Crabtree effect: replacing media glucose with galactose increases susceptibility of HepG2 cells to mitochondrial toxicants. Toxicol Sci. 2007;97(2):539–47.
Article
CAS
PubMed
Google Scholar
Karoulia Z, Gavathiotis E, Poulikakos PI. New perspectives for targeting RAF kinase in human cancer. Nat Rev Cancer. 2017;17(11):676–91.
Article
CAS
PubMed
PubMed Central
Google Scholar
McGuirk S, Audet-Delage Y, St-Pierre J. Metabolic Fitness and Plasticity in Cancer Progression. Trends in cancer. 2020;6(1):49–61.
Article
CAS
PubMed
Google Scholar
Xie H, Simon MC. Oxygen availability and metabolic reprogramming in cancer. J Biol Chem. 2017;292(41):16825–32.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ren YJ, Wang XH, Ji C, Guan YD, Lu XJ, Liu XR, et al. Silencing of NAC1 Expression Induces Cancer Cells Oxidative Stress in Hypoxia and Potentiates the Therapeutic Activity of Elesclomol. Front Pharmacol. 2017;8:804.
Article
PubMed
PubMed Central
CAS
Google Scholar
Tataranni T, Piccoli C. Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications. Oxid Med Cell Longev. 2019;2019:8201079.
Article
PubMed
PubMed Central
CAS
Google Scholar
Semenza GL. HIF-1: using two hands to flip the angiogenic switch. Cancer Metastasis Rev. 2000;19(1–2):59–65.
Article
CAS
PubMed
Google Scholar
Wu Z, Zuo M, Zeng L, Cui K, Liu B, Yan C, et al. OMA1 reprograms metabolism under hypoxia to promote colorectal cancer development. EMBO Rep. 2021;22(1):e50827.
Article
CAS
PubMed
Google Scholar
Hasinoff BB, Wu X, Yadav AA, Patel D, Zhang H, Wang DS, et al. Cellular mechanisms of the cytotoxicity of the anticancer drug elesclomol and its complex with Cu(II). Biochem Pharmacol. 2015;93(3):266–76.
Article
CAS
PubMed
Google Scholar
Gao W, Huang Z, Duan J, Nice EC, Lin J, Huang C. Elesclomol induces copper-dependent ferroptosis in colorectal cancer cells via degradation of ATP7A. Mol Oncol. 2021;15(12):3527–44.
Article
PubMed
PubMed Central
CAS
Google Scholar
Wu L, Zhou L, Liu DQ, Vogt FG, Kord AS. LC-MS/MS and density functional theory study of copper(II) and nickel(II) chelating complexes of elesclomol (a novel anticancer agent). J Pharm Biomed Anal. 2011;54(2):331–6.
Article
CAS
PubMed
Google Scholar
Fukai T, Ushio-Fukai M, Kaplan JH. Copper transporters and copper chaperones: roles in cardiovascular physiology and disease. Am J Physiol Cell Physiol. 2018;315(2):C186-c201.
Article
CAS
PubMed
PubMed Central
Google Scholar
Yadav AA, Patel D, Wu X, Hasinoff BB. Molecular mechanisms of the biological activity of the anticancer drug elesclomol and its complexes with Cu(II), Ni(II) and Pt(II). J Inorg Biochem. 2013;126:1–6.
Article
CAS
PubMed
Google Scholar
Foo BJ, Eu JQ, Hirpara JL, Pervaiz S. Interplay between Mitochondrial Metabolism and Cellular Redox State Dictates Cancer Cell Survival. Oxid Med Cell Longev. 2021;2021:1341604.
Article
PubMed
PubMed Central
CAS
Google Scholar
Bian M, Fan R, Zhao S, Liu W. Targeting the Thioredoxin System as a Strategy for Cancer Therapy. J Med Chem. 2019;62(16):7309–21.
Article
CAS
PubMed
Google Scholar
Niu B, Liao K, Zhou Y, Wen T, Quan G, Pan X, et al. Application of glutathione depletion in cancer therapy: Enhanced ROS-based therapy, ferroptosis, and chemotherapy. Biomaterials. 2021;277:121110.
Article
CAS
PubMed
Google Scholar
Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther. 2014;141(2):150–9.
Article
CAS
PubMed
Google Scholar
Rowland EA, Snowden CK, Cristea IM. Protein lipoylation: an evolutionarily conserved metabolic regulator of health and disease. Curr Opin Chem Biol. 2018;42:76–85.
Article
CAS
PubMed
Google Scholar
Harel M, Ortenberg R, Varanasi SK, Mangalhara KC, Mardamshina M, Markovits E, et al. Proteomics of Melanoma Response to Immunotherapy Reveals Mitochondrial Dependence. Cell. 2019;179(1):236-50.e18.
Article
CAS
PubMed
PubMed Central
Google Scholar
Jones RA, Robinson TJ, Liu JC, Shrestha M, Voisin V, Ju Y, et al. RB1 deficiency in triple-negative breast cancer induces mitochondrial protein translation. J Clin Investig. 2016;126(10):3739–57.
Article
PubMed
PubMed Central
Google Scholar
Birkenmeier K, Dröse S, Wittig I, Winkelmann R, Käfer V, Döring C, et al. Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma are highly dependent on oxidative phosphorylation. Int J Cancer. 2016;138(9):2231–46.
Article
CAS
PubMed
Google Scholar
Zhang Z, Li TE, Chen M, Xu D, Zhu Y, Hu BY, et al. MFN1-dependent alteration of mitochondrial dynamics drives hepatocellular carcinoma metastasis by glucose metabolic reprogramming. Br J Cancer. 2020;122(2):209–20.
Article
CAS
PubMed
Google Scholar
Gentric G, Kieffer Y, Mieulet V, Goundiam O, Bonneau C, Nemati F, et al. PML-Regulated Mitochondrial Metabolism Enhances Chemosensitivity in Human Ovarian Cancers. Cell Metab. 2019;29(1):156-73.e10.
Article
CAS
PubMed
PubMed Central
Google Scholar
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. 2012;22(4):547–60.
Article
CAS
PubMed
PubMed Central
Google Scholar
Viale A, Pettazzoni P, Lyssiotis CA, Ying H, Sánchez N, Marchesini M, et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature. 2014;514(7524):628–32.
Article
CAS
PubMed
PubMed Central
Google Scholar
Pastò A, Bellio C, Pilotto G, Ciminale V, Silic-Benussi M, Guzzo G, et al. Cancer stem cells from epithelial ovarian cancer patients privilege oxidative phosphorylation, and resist glucose deprivation. Oncotarget. 2014;5(12):4305–19.
Article
PubMed
PubMed Central
Google Scholar
Raggi C, Taddei ML, Sacco E, Navari N, Correnti M, Piombanti B, et al. Mitochondrial oxidative metabolism contributes to a cancer stem cell phenotype in cholangiocarcinoma. J Hepatol. 2021;74(6):1373–85.
Article
CAS
PubMed
Google Scholar
Lagadinou ED, Sach A, Callahan K, Rossi RM, Neering SJ, Minhajuddin M, et al. BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. Cell Stem Cell. 2013;12(3):329–41.
Article
CAS
PubMed
PubMed Central
Google Scholar
Gui CP, Wei JH, Chen YH, Fu LM, Tang YM, Cao JZ, et al. A new thinking: extended application of genomic selection to screen multiomics data for development of novel hypoxia-immune biomarkers and target therapy of clear cell renal cell carcinoma. Brief Bioinform. 2021;22(6):bbab173.
Article
PubMed
CAS
Google Scholar
Zhang B, Tang B, Gao J, Li J, Kong L, Qin L. A hypoxia-related signature for clinically predicting diagnosis, prognosis and immune microenvironment of hepatocellular carcinoma patients. J Transl Med. 2020;18(1):342.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bajaj J, Diaz E, Reya T. Stem cells in cancer initiation and progression. J Cell Biol. 2020;219(1):e201911053.
Article
PubMed
CAS
Google Scholar
Clara JA, Monge C, Yang Y, Takebe N. Targeting signalling pathways and the immune microenvironment of cancer stem cells - a clinical update. Nat Rev Clin Oncol. 2020;17(4):204–32.
Article
PubMed
Google Scholar
Denise C, Paoli P, Calvani M, Taddei ML, Giannoni E, Kopetz S, et al. 5-fluorouracil resistant colon cancer cells are addicted to OXPHOS to survive and enhance stem-like traits. Oncotarget. 2015;6(39):41706–21.
Article
PubMed
PubMed Central
Google Scholar
Matassa DS, Amoroso MR, Lu H, Avolio R, Arzeni D, Procaccini C, et al. Oxidative metabolism drives inflammation-induced platinum resistance in human ovarian cancer. Cell Death Differ. 2016;23(9):1542–54.
Article
CAS
PubMed
PubMed Central
Google Scholar
De Rosa V, Iommelli F, Monti M, Fonti R, Votta G, Stoppelli MP, et al. Reversal of Warburg Effect and Reactivation of Oxidative Phosphorylation by Differential Inhibition of EGFR Signaling Pathways in Non-Small Cell Lung Cancer. Clin Cancer Res. 2015;21(22):5110–20.
Article
PubMed
CAS
Google Scholar
Sun Y, Xu H, Chen X, Li X, Luo B. Inhibition of mitochondrial respiration overcomes hepatocellular carcinoma chemoresistance. Biochem Biophys Res Commun. 2019;508(2):626–32.
Article
CAS
PubMed
Google Scholar
Lim SM, Syn NL, Cho BC, Soo RA. Acquired resistance to EGFR targeted therapy in non-small cell lung cancer: Mechanisms and therapeutic strategies. Cancer Treat Rev. 2018;65:1–10.
Article
CAS
PubMed
Google Scholar
Pelicano H, Martin DS, Xu RH, Huang P. Glycolysis inhibition for anticancer treatment. Oncogene. 2006;25(34):4633–46.
Article
CAS
PubMed
Google Scholar
Zhang D, Li J, Wang F, Hu J, Wang S, Sun Y. 2-Deoxy-D-glucose targeting of glucose metabolism in cancer cells as a potential therapy. Cancer Lett. 2014;355(2):176–83.
Article
CAS
PubMed
Google Scholar
Varshney R, Dwarakanath B, Jain V. Radiosensitization by 6-aminonicotinamide and 2-deoxy-D-glucose in human cancer cells. Int J Radiat Biol. 2005;81(5):397–408.
Article
CAS
PubMed
Google Scholar
Shoshan MC. 3-Bromopyruvate: targets and outcomes. J Bioenerg Biomembr. 2012;44(1):7–15.
Article
CAS
PubMed
Google Scholar
Modica-Napolitano JS, Bharath LP, Hanlon AJ, Hurley LD. The Anticancer Agent Elesclomol Has Direct Effects on Mitochondrial Bioenergetic Function in Isolated Mammalian Mitochondria. Biomolecules. 2019;9(8):298.
Article
CAS
PubMed Central
Google Scholar