Targeting Casein Kinase 1 (CK1) in Hematological Cancers.
AML
CK1α
CK1ε
CLL
MM
WNT pathway
casein kinase 1
inhibitors
leukemia
umbralisib
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
27 Nov 2020
27 Nov 2020
Historique:
received:
24
10
2020
revised:
20
11
2020
accepted:
21
11
2020
entrez:
2
12
2020
pubmed:
3
12
2020
medline:
5
3
2021
Statut:
epublish
Résumé
The casein kinase 1 enzymes (CK1) form a family of serine/threonine kinases with seven CK1 isoforms identified in humans. The most important substrates of CK1 kinases are proteins that act in the regulatory nodes essential for tumorigenesis of hematological malignancies. Among those, the most important are the functions of CK1s in the regulation of Wnt pathways, cell proliferation, apoptosis and autophagy. In this review we summarize the recent developments in the understanding of biology and therapeutic potential of the inhibition of CK1 isoforms in the pathogenesis of chronic lymphocytic leukemia (CLL), other non-Hodgkin lymphomas (NHL), myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and multiple myeloma (MM). CK1δ/ε inhibitors block CLL development in preclinical models via inhibition of WNT-5A/ROR1-driven non-canonical Wnt pathway. While no selective CK1 inhibitors have reached clinical stage to date, one dual PI3Kδ and CK1ε inhibitor, umbralisib, is currently in clinical trials for CLL and NHL patients. In MDS, AML and MM, inhibition of CK1α, acting via activation of p53 pathway, showed promising preclinical activities and the first CK1α inhibitor has now entered the clinical trials.
Identifiants
pubmed: 33261128
pii: ijms21239026
doi: 10.3390/ijms21239026
pmc: PMC7730698
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Casein Kinase I
EC 2.7.11.1
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Czech Science Foundation
ID : GX19-28347X
Organisme : Ministry of Education, Youth and Sports of the CR
ID : CZ.02.1.01/0.0/0.0/16_025/0007381
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