Targeting CK2 in cancer: a valuable strategy or a waste of time?


Journal

Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035

Informations de publication

Date de publication:
29 Oct 2021
Historique:
received: 13 09 2021
accepted: 12 10 2021
revised: 22 09 2021
entrez: 30 10 2021
pubmed: 31 10 2021
medline: 31 10 2021
Statut: epublish

Résumé

CK2 is a protein kinase involved in several human diseases (ranging from neurological and cardiovascular diseases to autoimmune disorders, diabetes, and infections, including COVID-19), but its best-known implications are in cancer, where it is considered a pharmacological target. Several CK2 inhibitors are available and clinical trials are underway in different cancer types. Recently, the suitability of CK2 as a broad anticancer target has been questioned by the finding that a newly developed compound, named SGC-CK2-1, which is more selective than any other known CK2 inhibitor, is poorly effective in reducing cell growth in different cancer lines, prompting the conclusion that the anticancer efficacy of CX-4945, the commonly used clinical-grade CK2 inhibitor, is to be attributed to its off-target effects. Here we perform a detailed scrutiny of published studies on CK2 targeting and a more in-depth analysis of the available data on SGC-CK2-1 vs. CX-4945 efficacy, providing a different perspective about the actual reliance of cancer cells on CK2. Collectively taken, our arguments would indicate that the pretended dispensability of CK2 in cancer is far from having been proved and warn against premature conclusions, which could discourage ongoing investigations on a potentially valuable drug target.

Identifiants

pubmed: 34716311
doi: 10.1038/s41420-021-00717-4
pii: 10.1038/s41420-021-00717-4
pmc: PMC8555718
doi:

Types de publication

Journal Article Review

Langues

eng

Pagination

325

Subventions

Organisme : AFM-Téléthon (French Muscular Dystrophy Association)
ID : 22974
Organisme : Fondazione per la Ricerca sulla Fibrosi Cistica (Fondazione FFC)
ID : FFC#11/2019
Organisme : Fondazione per la Ricerca sulla Fibrosi Cistica (Fondazione FFC)
ID : FFC#12/2017
Organisme : Università degli Studi di Padova (University of Padova)
ID : BORG_BIRD2121_01
Organisme : Associazione Italiana per la Ricerca sul Cancro (Italian Association for Cancer Research)
ID : IG 18756

Informations de copyright

© 2021. The Author(s).

Références

Cancers (Basel). 2021 Apr 02;13(7):
pubmed: 33918235
Prostate. 2010 Feb 1;70(2):126-34
pubmed: 19760628
Am J Pathol. 2016 Dec;186(12):3297-3315
pubmed: 27746184
Signal Transduct Target Ther. 2021 May 17;6(1):183
pubmed: 33994545
Oncol Rep. 2017 Feb;37(2):1141-1147
pubmed: 27959425
Biomedicines. 2021 May 18;9(5):
pubmed: 34070147
Cell Chem Biol. 2021 Apr 15;28(4):546-558.e10
pubmed: 33484635
Cancer Lett. 1996 Mar 19;101(1):31-5
pubmed: 8625279
J Med Chem. 2021 Apr 22;64(8):5082-5098
pubmed: 33834781
Nat Commun. 2017 Jan 17;8:14013
pubmed: 28094268
Cell Mol Life Sci. 2009 Jun;66(11-12):1858-67
pubmed: 19387548
Cell Oncol (Dordr). 2020 Dec;43(6):1003-1016
pubmed: 33052585
Cancer Res. 2010 Dec 15;70(24):10288-98
pubmed: 21159648
J Exp Clin Cancer Res. 2019 Jul 5;38(1):287
pubmed: 31277672
Cell Mol Life Sci. 2014 Aug;71(16):3173-85
pubmed: 24442476
Eur J Med Chem. 2021 Mar 15;214:113217
pubmed: 33548633
Mol Cell Biochem. 2017 Dec;436(1-2):87-97
pubmed: 28744813
Int J Oncol. 2016 Jun;48(6):2445-52
pubmed: 27098015
BMC Cancer. 2010 Aug 19;10:440
pubmed: 20718998
J Transl Med. 2011 Jun 25;9:97
pubmed: 21702981
Cell Death Dis. 2012 Feb 09;3:e271
pubmed: 22318540
Biochem Biophys Res Commun. 2020 Oct 20;531(3):409-415
pubmed: 32800562
Sci Adv. 2019 Jan 23;5(1):eaau9060
pubmed: 30746467
Blood. 2006 Sep 1;108(5):1698-707
pubmed: 16684960
Oncotarget. 2016 Sep 20;7(38):61789-61805
pubmed: 27557516
Mol Med. 1995 Sep;1(6):659-66
pubmed: 8529132
Mol Cancer Ther. 2014 Aug;13(8):2018-29
pubmed: 24867250
Methods Enzymol. 2010;484:495-514
pubmed: 21036247
Biofactors. 2010 May-Jun;36(3):187-95
pubmed: 20533398
Cancer Res. 2013 Apr 1;73(7):2289-97
pubmed: 23358686
Cells. 2021 Jan 18;10(1):
pubmed: 33477590
Gastric Cancer. 2019 Nov;22(6):1153-1163
pubmed: 31098863
Mol Cell Biochem. 2011 Oct;356(1-2):21-35
pubmed: 21761204
Biochim Biophys Acta. 2010 Mar;1804(3):499-504
pubmed: 19665589
J Med Chem. 2011 Jan 27;54(2):635-54
pubmed: 21174434
Cell. 2020 Aug 6;182(3):685-712.e19
pubmed: 32645325
Sci Rep. 2017 Nov 23;7(1):16134
pubmed: 29170453
Clin Cancer Res. 2010 Apr 15;16(8):2295-307
pubmed: 20371694
Oncogenesis. 2019 Oct 22;8(11):61
pubmed: 31641101
PLoS One. 2012;7(11):e49193
pubmed: 23145120
Oncogene. 2007 Oct 18;26(48):6915-26
pubmed: 17486073
J Neurooncol. 2017 Apr;132(2):219-229
pubmed: 28181105
Blood. 2010 Oct 14;116(15):2724-31
pubmed: 20660292
Semin Oncol. 2018 Jan;45(1-2):58-67
pubmed: 30318085
J Hematol Oncol. 2013 Oct 12;6:78
pubmed: 24283803
Oncogene. 2015 Jul;34(28):3688-99
pubmed: 25241897
Breast Cancer Res. 2015;17:19
pubmed: 25837326
PLoS One. 2015 Dec 04;10(12):e0144126
pubmed: 26637171
Trends Pharmacol Sci. 2021 May;42(5):313-315
pubmed: 33771354
Cell Mol Life Sci. 2009 Jun;66(11-12):1817-29
pubmed: 19387552
Oncotarget. 2015 Oct 27;6(33):34800-17
pubmed: 26430962
PLoS One. 2017 Dec 4;12(12):e0188854
pubmed: 29206231
Mol Oncol. 2013 Dec;7(6):1103-15
pubmed: 24012109
Oncol Rep. 2013 Jul;30(1):377-84
pubmed: 23595577
Anticancer Res. 2015 Mar;35(3):1537-42
pubmed: 25750308
Int J Mol Sci. 2019 Nov 26;20(23):
pubmed: 31779225
Sci Rep. 2017 Feb 17;7:42409
pubmed: 28209983
J Biol Chem. 2016 Aug 19;291(34):17804-15
pubmed: 27226552
Nature. 2020 Jul;583(7816):459-468
pubmed: 32353859
PLoS One. 2014 Dec 26;9(12):e115609
pubmed: 25541719

Auteurs

Mauro Salvi (M)

Deptartment Biomedical Sciences, University of Padova, Padova, Italy.

Christian Borgo (C)

Deptartment Biomedical Sciences, University of Padova, Padova, Italy.

Lorenzo A Pinna (LA)

Deptartment Biomedical Sciences, University of Padova, Padova, Italy. lorenzo.pinna@unipd.it.
CNR Neuroscience Institute, 35131, Padova, Italy. lorenzo.pinna@unipd.it.

Maria Ruzzene (M)

Deptartment Biomedical Sciences, University of Padova, Padova, Italy. maria.ruzzene@unipd.it.
CNR Neuroscience Institute, 35131, Padova, Italy. maria.ruzzene@unipd.it.

Classifications MeSH