The XPO1 Inhibitor KPT-8602 Synergizes with Dexamethasone in Acute Lymphoblastic Leukemia.
Animals
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Cell Line, Tumor
Cell Proliferation
/ drug effects
Dexamethasone
/ pharmacology
Doxorubicin
/ pharmacology
Drug Synergism
Humans
Karyopherins
/ antagonists & inhibitors
Mice
Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ drug therapy
Receptors, Cytoplasmic and Nuclear
/ antagonists & inhibitors
Vincristine
/ pharmacology
Xenograft Model Antitumor Assays
Exportin 1 Protein
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 2020
01 11 2020
Historique:
received:
15
04
2020
revised:
20
07
2020
accepted:
18
08
2020
pubmed:
23
8
2020
medline:
27
11
2021
entrez:
23
8
2020
Statut:
ppublish
Résumé
KPT-8602 (Eltanexor) is a second-generation exportin-1 (XPO1) inhibitor with potent activity against acute lymphoblastic leukemia (ALL) in preclinical models and with minimal effects on normal cells. In this study, we evaluated whether KPT-8602 would synergize with dexamethasone, vincristine, or doxorubicin, three drugs currently used for the treatment of ALL. First, we searched for the most synergistic combination of KPT-8602 with dexamethasone, vincristine, or doxorubicin KPT-8602 showed strong synergism with dexamethasone on human B-ALL and T-ALL cell lines as well as Our preclinical study demonstrates that KPT-8602 enhances the effects of dexamethasone to inhibit B-ALL and T-ALL cells via NR3C1- and E2F-mediated transcriptional complexes, allowing to achieve increased dexamethasone effects for patients.
Identifiants
pubmed: 32826328
pii: 1078-0432.CCR-20-1315
doi: 10.1158/1078-0432.CCR-20-1315
doi:
Substances chimiques
Antineoplastic Agents
0
Karyopherins
0
Receptors, Cytoplasmic and Nuclear
0
Vincristine
5J49Q6B70F
Dexamethasone
7S5I7G3JQL
Doxorubicin
80168379AG
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5747-5758Informations de copyright
©2020 American Association for Cancer Research.
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