Targeting Casein Kinase 1 (CK1) in Hematological Cancers

0540072 - BFÚ 2021 RIV CH eng J - Journal Article
Janovská, P. - Normant, E. - Miskin, H. - Bryja, Vítězslav
Targeting Casein Kinase 1 (CK1) in Hematological Cancers.
International Journal of Molecular Sciences. Roč. 21, č. 23 (2020), č. článku 9026. E-ISSN 1422-0067
Institutional support: RVO:68081707
Keywords : casein kinase 1 * CK1 * leukemia * CLL * aml * MM
OECD category: Biochemistry and molecular biology
Impact factor: 5.924, year: 2020
Method of publishing: Open access
https://www.mdpi.com/1422-0067/21/23/9026

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). CK1 delta/epsilon 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 PI3K delta and CK1 epsilon inhibitor, umbralisib, is currently in clinical trials for CLL and NHL patients. In MDS, AML and MM, inhibition of CK1 alpha, acting via activation of p53 pathway, showed promising preclinical activities and the first CK1 alpha inhibitor has now entered the clinical trials.
Permanent Link: http://hdl.handle.net/11104/0317737