A Novel Mitochondrial Inhibitor Blocks MAPK Pathway and Overcomes MAPK Inhibitor Resistance in Melanoma.
AMP-Activated Protein Kinase Kinases
Animals
Cell Line, Tumor
Drug Resistance, Neoplasm
/ drug effects
Gene Expression Regulation, Neoplastic
/ drug effects
Heterografts
Humans
MAP Kinase Signaling System
/ drug effects
Melanoma
/ drug therapy
Mice
Mitochondria
/ drug effects
Oxadiazoles
/ therapeutic use
Oxidative Phosphorylation
/ drug effects
Piperidines
/ therapeutic use
Positron-Emission Tomography
Protein Kinase Inhibitors
/ pharmacology
Protein Kinases
/ genetics
Proto-Oncogene Proteins B-raf
/ genetics
TOR Serine-Threonine Kinases
/ genetics
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 11 2019
01 11 2019
Historique:
received:
12
03
2019
revised:
25
06
2019
accepted:
09
08
2019
pubmed:
24
8
2019
medline:
9
9
2020
entrez:
24
8
2019
Statut:
ppublish
Résumé
The purpose of this study is to determine if inhibition of mitochondrial oxidative phosphorylation (OxPhos) is an effective strategy against MAPK pathway inhibitor (MAPKi)-resistant BRAF-mutant melanomas. OPi potently inhibited OxPhos and the Targeting OxPhos with OPi has significant antitumor activity in MAPKi-resistant, BRAF-mutant melanomas, and merits further clinical investigation as a potential new strategy to overcome intrinsic and acquired resistance to MAPKi in patients.
Identifiants
pubmed: 31439581
pii: 1078-0432.CCR-19-0836
doi: 10.1158/1078-0432.CCR-19-0836
pmc: PMC6825560
mid: NIHMS1537664
doi:
Substances chimiques
IACS-010759
0
Oxadiazoles
0
Piperidines
0
Protein Kinase Inhibitors
0
Protein Kinases
EC 2.7.-
MTOR protein, human
EC 2.7.1.1
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
TOR Serine-Threonine Kinases
EC 2.7.11.1
AMP-Activated Protein Kinase Kinases
EC 2.7.11.3
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6429-6442Subventions
Organisme : NCI NIH HHS
ID : P50 CA094056
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA016672
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA231506
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000371
Pays : United States
Organisme : NCATS NIH HHS
ID : TL1 TR000369
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009666
Pays : United States
Informations de copyright
©2019 American Association for Cancer Research.
Références
J Transl Med. 2011 May 24;9:76
pubmed: 21609436
Mol Cell. 2013 Oct 24;52(2):161-72
pubmed: 24095280
Cancer Discov. 2018 May;8(5):568-581
pubmed: 29496664
Sci Transl Med. 2013 Jul 31;5(196):196ra98
pubmed: 23903755
J Clin Invest. 2001 Oct;108(8):1167-74
pubmed: 11602624
Cell Rep. 2017 Nov 14;21(7):1953-1967
pubmed: 29141225
Mol Cell Oncol. 2015 Jan 23;2(3):e991610
pubmed: 27308473
Cancer Discov. 2018 May;8(5):556-567
pubmed: 29496665
Nat Med. 2018 Jul;24(7):1047-1057
pubmed: 29892061
Mol Oncol. 2016 Jan;10(1):73-84
pubmed: 26365896
Cell Metab. 2018 May 01;27(5):977-987.e4
pubmed: 29628419
Clin Sci (Lond). 2018 Mar 9;132(5):543-568
pubmed: 29523752
Sci Rep. 2017 Nov 10;7(1):15285
pubmed: 29127321
Cancer Discov. 2019 May;9(5):628-645
pubmed: 30787016
Cancer Res. 2010 Nov 1;70(21):8736-47
pubmed: 20959481
Cancer Res. 2014 Dec 1;74(23):7037-47
pubmed: 25297634
N Engl J Med. 2015 Jan 1;372(1):30-9
pubmed: 25399551
Proc Natl Acad Sci U S A. 2011 May 24;108(21):8674-9
pubmed: 21555572
Nat Genet. 2007 Mar;39(3):347-51
pubmed: 17293865
Cancer Cell. 2013 Mar 18;23(3):302-15
pubmed: 23477830
Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18226-31
pubmed: 24145418
Pigment Cell Melanoma Res. 2012 Mar;25(2):248-58
pubmed: 22171948
Nature. 2011 Nov 20;481(7381):385-8
pubmed: 22101431
Lancet Oncol. 2016 Dec;17(12):1743-1754
pubmed: 27864013
Cell Rep. 2014 Jun 12;7(5):1679-1690
pubmed: 24857658
Nature. 2005 Jul 7;436(7047):117-22
pubmed: 16001072
J Nucl Med. 2017 Aug;58(8):1224-1229
pubmed: 28209906
Biochem Pharmacol. 2014 Feb 1;87(3):381-9
pubmed: 24291778
Nat Med. 2018 Jul;24(7):1036-1046
pubmed: 29892070
Clin Cancer Res. 2009 Dec 15;15(24):7538-7546
pubmed: 19996208
Br J Cancer. 2008 Oct 21;99(8):1265-8
pubmed: 18813315
N Engl J Med. 2014 Nov 13;371(20):1877-88
pubmed: 25265492
N Engl J Med. 2014 Nov 13;371(20):1867-76
pubmed: 25265494
Cancer Cell. 2013 Mar 18;23(3):287-301
pubmed: 23416000