From the Inventor/Co-Founder
Hayat U, Elliott GT, Olszanski AJ, Altieri DC. Feasibility and safety of targeting mitochondria for cancer therapy - preclinical characterization of gamitrinib, a first-in-class, mitochondriaL-targeted small molecule Hsp90 inhibitor. Cancer Biol Ther. 2022 Dec 31;23(1):117-126.
Reyes-Uribe P, Adrianzen-Ruesta MP, Deng Z, Echevarria-Vargas I, Mender I, Saheb S, Liu Q, Altieri DC, Murphy ME, Shay JW, Lieberman PM, Villanueva J. Exploiting TERT dependency as a therapeutic strategy for NRAS-mutant melanoma. Oncogene. 2018 Jul;37(30):4058-4072.
Boucherat O, Peterlini T, Bourgeois A, Nadeau V, Breuils-Bonnet S, Boilet-Molez S, Potus F, Meloche J, Chabot S, Lambert C, Tremblay E, Chae YC, Altieri DC, Sutendra G, Michelakis ED, Paulin R, Provencher S, Bonnet S. Mitochondrial HSP90 Accumulation Promotes Vascular Remodeling in Pulmonary Arterial Hypertension. Am J Respir Crit Care Med. 2018 Jul 1;198(1):90-103.
Karpel-Massler G, Ishida CT, Bianchetti E, Shu C, Perez-Lorenzo R, Horst B, Banu M, Roth KA, Bruce JN, Canoll P, Altieri DC, Siegelin MD. Inhibition of Mitochondrial Matrix Chaperones and Antiapoptotic Bcl-2 Family Proteins Empower Antitumor Therapeutic Responses. Cancer Res. 2017 Jul 1;77(13):3513-3526.
Ishida CT, Shu C, Halatsch ME, Westhoff MA, Altieri DC, Karpel-Massler G, Siegelin MD. Mitochondrial matrix chaperone and c-myc inhibition causes enhanced lethality in glioblastoma. Oncotarget. 2017 Jun 6;8(23):37140-37153.
Zhang G, Frederick DT, Wu L, Wei Z, Krepler C, Srinivasan S, Chae YC, Xu X, Choi H, Dimwamwa E, Ope O, Shannan B, Basu D, Zhang D, Guha M, Xiao M, Randell S, Sproesser K, Xu W, Liu J, Karakousis GC, Schuchter LM, Gangadhar TC, Amaravadi RK, Gu M, Xu C, Ghosh A, Xu W, Tian T, Zhang J, Zha S, Liu Q, Brafford P, Weeraratna A, Davies MA, Wargo JA, Avadhani NG, Lu Y, Mills GB, Altieri DC, Flaherty KT, Herlyn M. Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors. J Clin Invest. 2016 May 2;126(5):1834-56.
Caino MC, Chae YC, Vaira V, Ferrero S, Nosotti M, Martin NM, Weeraratna A, O'Connell M, Jernigan D, Fatatis A, Languino LR, Bosari S, Altieri DC. Metabolic stress regulates cytoskeletal dynamics and metastasis of cancer cells. J Clin Invest. 2013 Jul;123(7):2907-20.
Chae YC, Caino MC, Lisanti S, Ghosh JC, Dohi T, Danial NN, Villanueva J, Ferrero S, Vaira V, Santambrogio L, Bosari S, Languino LR, Herlyn M, Altieri DC. Control of tumor bioenergetics and survival stress signaling by mitochondrial HSP90s. Cancer Cell. 2012 Sep 11;22(3):331-44.
Kang BH, Tavecchio M, Goel HL, Hsieh CC, Garlick DS, Raskett CM, Lian JB, Stein GS, Languino LR, Altieri DC. Targeted inhibition of mitochondrial Hsp90 suppresses localised and metastatic prostate cancer growth in a genetic mouse model of disease. Br J Cancer. 2011 Feb 15;104(4):629-34.
Siegelin MD, Dohi T, Raskett CM, Orlowski GM, Powers CM, Gilbert CA, Ross AH, Plescia J, Altieri DC. Exploiting the mitochondrial unfolded protein response for cancer therapy in mice and human cells. J Clin Invest. 2011 Apr;121(4):1349-60.
Leav I, Plescia J, Goel HL, Li J, Jiang Z, Cohen RJ, Languino LR, Altieri DC. Cytoprotective mitochondrial chaperone TRAP-1 as a novel molecular target in localized and metastatic prostate cancer. Am J Pathol. 2010 Jan;176(1):393-401.
Kang BH, Plescia J, Song HY, Meli M, Colombo G, Beebe K, Scroggins B, Neckers L, Altieri DC. Combinatorial drug design targeting multiple cancer signaling networks controlled by mitochondrial Hsp90. J Clin Invest. 2009 Mar;119(3):454-64.
Independent Publications (not involving Dr. Altieri)
Tsai HY, Bronner MP, March JK, Valentine JF, Shroyer NF, Lai LA, Brentnall TA, Pan S, Chen R. Metabolic targeting of NRF2 potentiates the efficacy of the TRAP1 inhibitor G-TPP through reduction of ROS detoxification in colorectal cancer. Cancer Lett. 2022 Nov 28;549:215915. doi: 10.1016/j.canlet.2022.215915.
Wei S, Yin D, Yu S, Lin X, Savani MR, Du K, Ku Y, Wu D, Li S, Liu H, Tian M, Chen Y, Bowie M, Hariharan S, Waitkus M, Keir ST, Sugarman ET, Deek RA, Labrie M, Khasraw M, Lu Y, Mills GB, Herlyn M, Wu K, Liu L, Wei Z, Flaherty KT, Abdullah K, Zhang G, Ashley DM. Antitumor Activity of a Mitochondrial-Targeted HSP90 Inhibitor in Gliomas. Clin Cancer Res. 2022 May 13;28(10):2180-2195.
Zhang J, Li H, Liu Y, Zhao K, Wei S, Sugarman ET, Liu L, Zhang G. Targeting HSP90 as a Novel Therapy for Cancer: Mechanistic Insights and Translational Relevance. Cells. 2022 Sep 6;11(18):2778.
Wang N, Zhu P, Huang R, Sun L, Dong D, Gao Y. Suppressing TRAP1 sensitizes glioblastoma multiforme cells to temozolomide. Exp Ther Med. 2021 Nov;22(5):1246.
Zhang Y, Nguyen TTT, Shang E, Mela A, Humala N, Mahajan A, Zhao J, Shu C, Torrini C, Sanchez-Quintero MJ, Kleiner G, Bianchetti E, Westhoff MA, Quinzii CM, Karpel-Massler G, Bruce JN, Canoll P, Siegelin MD. MET Inhibition Elicits PGC1α-Dependent Metabolic Reprogramming in Glioblastoma. Cancer Res. 2020 Jan 1;80(1):30-43. doi: 10.1158/0008-5472.CAN-19-1389.
Nguyen TTT, Zhang Y, Shang E, Shu C, Quinzii CM, Westhoff MA, Karpel-Massler G, Siegelin MD. Inhibition of HDAC1/2 Along with TRAP1 Causes Synthetic Lethality in Glioblastoma Model Systems. Cells. 2020 Jul 10;9(7):1661. doi: 10.3390/cells9071661. PMID: 32664214; PMCID: PMC7407106.
Nguyen TTT, Ishida CT, Shang E, Shu C, Bianchetti E, Karpel-Massler G, Siegelin MD. Activation of LXR Receptors and Inhibition of TRAP1 Causes Synthetic Lethality in Solid Tumors. Cancers (Basel). 2019 Jun 7;11(6):788.
Vo VTA, Choi JW, Phan ANH, Hua TNM, Kim MK, Kang BH, Jung SH, Yong SJ, Jeong Y. TRAP1 Inhibition Increases Glutamine Synthetase Activity in Glutamine Auxotrophic Non-small Cell Lung Cancer Cells. Anticancer Res. 2018 Apr;38(4):2187-2193.
Kim S, Koh H. Role of FOXO transcription factors in crosstalk between mitochondria and the nucleus. J Bioenerg Biomembr. 2017 Aug;49(4):335-341.
Palladino G, Notarangelo T, Pannone G, Piscazzi A, Lamacchia O, Sisinni L, Spagnoletti G, Toti P, Santoro A, Storto G, Bufo P, Cignarelli M, Esposito F, Landriscina M. TRAP1 regulates cell cycle and apoptosis in thyroid carcinoma cells. Endocr Relat Cancer. 2016 Sep;23(9):699-709.
Lebedev I, Nemajerova A, Foda ZH, Kornaj M, Tong M, Moll UM, Seeliger MA. A Novel In Vitro CypD-Mediated p53 Aggregation Assay Suggests a Model for Mitochondrial Permeability Transition by Chaperone Systems. J Mol Biol. 2016 Oct 9;428(20):4154-4167.
Kim H, Yang J, Kim MJ, Choi S, Chung JR, Kim JM, Yoo YH, Chung J, Koh H. Tumor Necrosis Factor Receptor-associated Protein 1 (TRAP1) Mutation and TRAP1 Inhibitor Gamitrinib-triphenylphosphonium (G-TPP) Induce a Forkhead Box O (FOXO)-dependent Cell Protective Signal from Mitochondria. J Biol Chem. 2016 Jan 22;291(4):1841-1853.
Yoo SH, Kim HY, Rho JH, Jeong SY, Yun J, Yun I, Park HT, Yoo YH. Targeted inhibition of mitochondrial Hsp90 induces mitochondrial elongation in Hep3B hepatocellular carcinoma cells undergoing apoptosis by increasing the ROS level. Int J Oncol. 2015 Nov;47(5):1783-92.
Condelli V, Maddalena F, Sisinni L, Lettini G, Matassa DS, Piscazzi A, Palladino G, Amoroso MR, Esposito F, Landriscina M. Targeting TRAP1 as a downstream effector of BRAF cytoprotective pathway: a novel strategy for human BRAF-driven colorectal carcinoma. Oncotarget. 2015 Sep 8;6(26):22298-309.
Park HK, Lee JE, Lim J, Kang BH. Mitochondrial Hsp90s suppress calcium-mediated stress signals propagating from mitochondria to the ER in cancer cells. Mol Cancer. 2014 Jun 12;13:148.
Maddalena F, Sisinni L, Lettini G, Condelli V, Matassa DS, Piscazzi A, Amoroso MR, La Torre G, Esposito F, Landriscina M. Resistance to paclitaxel in breast carcinoma cells requires a quality control of mitochondrial antiapoptotic proteins by TRAP1. Mol Oncol. 2013 Oct;7(5):895-906.
Yan C, Oh JS, Yoo SH, Lee JS, Yoon YG, Oh YJ, Jang MS, Lee SY, Yang J, Lee SH, Kim HY, Yoo YH. The targeted inhibition of mitochondrial Hsp90 overcomes the apoptosis resistance conferred by Bcl-2 in Hep3B cells via necroptosis. Toxicol Appl Pharmacol. 2013 Jan 1;266(1):9-18.
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