Dual Inhibition of FLT3 and AXL by Gilteritinib Overcomes Hematopoietic Niche-Driven Resistance Mechanisms in
Aniline Compounds
/ pharmacology
Benzothiazoles
/ pharmacology
Cell Line, Tumor
Drug Resistance, Neoplasm
/ drug effects
Hematopoiesis
Humans
Leukemia, Myeloid, Acute
/ drug therapy
Phenylurea Compounds
/ pharmacology
Proto-Oncogene Proteins
/ antagonists & inhibitors
Pyrazines
/ pharmacology
Receptor Protein-Tyrosine Kinases
/ antagonists & inhibitors
fms-Like Tyrosine Kinase 3
/ antagonists & inhibitors
Axl Receptor Tyrosine Kinase
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 2021
01 11 2021
Historique:
received:
07
08
2020
revised:
14
06
2021
accepted:
11
08
2021
pubmed:
18
8
2021
medline:
1
4
2022
entrez:
17
8
2021
Statut:
ppublish
Résumé
AXL has been shown to play a pivotal role in the selective response of Herein, we compared the effect of dual FLT3/AXL-TKI gilteritinib with quizartinib through We observed that gilteritinib maintained a stronger proapoptotic effect in hypoxia and coculture with bone marrow stromal cells compared with quizartinib, linked to a dose-dependent inhibition of AXL phosphorylation. Overall, these findings suggest that gilteritinib as a single agent, compared with quizartinib, is more likely to reach leukemic cells in their protective microenvironment, particularly AML clones highly dependent on
Identifiants
pubmed: 34400415
pii: 1078-0432.CCR-20-3114
doi: 10.1158/1078-0432.CCR-20-3114
doi:
Substances chimiques
Aniline Compounds
0
Benzothiazoles
0
Phenylurea Compounds
0
Proto-Oncogene Proteins
0
Pyrazines
0
gilteritinib
0
quizartinib
7LA4O6Q0D3
FLT3 protein, human
EC 2.7.10.1
Receptor Protein-Tyrosine Kinases
EC 2.7.10.1
fms-Like Tyrosine Kinase 3
EC 2.7.10.1
Axl Receptor Tyrosine Kinase
0
AXL protein, human
0
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6012-6025Informations de copyright
©2021 American Association for Cancer Research.
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