GZ17-6.02 and Pemetrexed Interact to Kill Osimertinib-Resistant NSCLC Cells That Express Mutant ERBB1 Proteins.
EGFR
ER stress
GZ17-6.02
NSCLC
autophagy
osimertinib
pemetrexed
resistance
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2021
2021
Historique:
received:
17
05
2021
accepted:
29
07
2021
entrez:
7
9
2021
pubmed:
8
9
2021
medline:
8
9
2021
Statut:
epublish
Résumé
We determined the molecular mechanisms by which the novel therapeutic GZ17-6.02 killed non-small cell lung cancer (NSCLC) cells. Erlotinib, afatinib, and osimertinib interacted with GZ17-6.02 to kill NSCLC cells expressing mutant EGFR proteins. GZ17-6.02 did not interact with any EGFR inhibitor to kill osimertinib-resistant cells. GZ17-6.02 interacted with the thymidylate synthase inhibitor pemetrexed to kill NSCLC cells expressing mutant ERBB1 proteins or mutant RAS proteins or cells that were resistant to EGFR inhibitors. The drugs interacted to activate ATM, the AMPK, and ULK1 and inactivate mTORC1, mTORC2, ERK1/2, AKT, eIF2α; and c-SRC. Knockdown of ATM or AMPKα
Identifiants
pubmed: 34490108
doi: 10.3389/fonc.2021.711043
pmc: PMC8417372
doi:
Types de publication
Journal Article
Langues
eng
Pagination
711043Informations de copyright
Copyright © 2021 Booth, West, Moore, Von Hoff and Dent.
Déclaration de conflit d'intérêts
PD has received funding from Genzada Pharmaceuticals Inc. PM and CW are paid officers of the company. PD and DH are key company scientific advisors/consultants. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest
Références
Adv Exp Med Biol. 2021;1286:49-64
pubmed: 33725344
Oncotarget. 2017 Oct 9;8(52):90262-90277
pubmed: 29163826
Cancer Manag Res. 2021 Feb 25;13:2025-2032
pubmed: 33658860
Transl Lung Cancer Res. 2021 Feb;10(2):1165-1185
pubmed: 33718054
Cancer Res. 2021 Jun 1;81(11):3051-3066
pubmed: 33727228
Cancer Res. 2010 Dec 15;70(24):10299-309
pubmed: 21159649
Pharmgenomics Pers Med. 2021 Mar 09;14:301-317
pubmed: 33727854
Oncogene. 2019 Jul;38(30):5890-5904
pubmed: 31253872
J Cell Physiol. 2020 Nov;235(11):7889-7899
pubmed: 31912905
Front Oncol. 2020 Sep 02;10:1331
pubmed: 32983965
Thorac Cancer. 2021 Apr;12(7):1096-1105
pubmed: 33565276
Phytother Res. 2010 Jan;24(1):146-9
pubmed: 19548284
Sci Rep. 2018 Aug 15;8(1):12163
pubmed: 30111862
Oncotarget. 2016 Apr 12;7(15):19620-30
pubmed: 26934000
Cancer Res. 2011 Jul 15;71(14):4955-67
pubmed: 21622715
Oncotarget. 2017 Jan 3;8(1):1449-1468
pubmed: 27903966
Oncotarget. 2016 Apr 26;7(17):23608-32
pubmed: 27015562
J Dermatolog Treat. 2020 May 20;:1-2
pubmed: 32362152
Aging (Albany NY). 2021 Feb 17;13(5):6890-6903
pubmed: 33621951
Ann Oncol. 2020 Nov;31(11):1536-1544
pubmed: 32861806
J Cell Physiol. 2020 Nov;235(11):8098-8113
pubmed: 31951027
J Ethnopharmacol. 2016 Jul 1;187:104-22
pubmed: 27125594
Biochem Biophys Res Commun. 2004 Apr 23;317(1):128-32
pubmed: 15047157
Recent Pat Anticancer Drug Discov. 2021 Jan 19;:
pubmed: 33494684
Oncotarget. 2017 May 17;8(47):83155-83170
pubmed: 29137331
Mutat Res. 2002 Mar 20;500(1-2):39-48
pubmed: 11890933
J Ethnopharmacol. 2017 May 5;203:127-162
pubmed: 28359849
Oncotarget. 2017 Mar 7;8(10):16367-16386
pubmed: 28146421