Dinaciclib synergizes with BH3 mimetics targeting BCL-2 and BCL-X
BCL-2 proteins
BH3 mimetics
CDK inhibitors
cell death
multiple myeloma
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
revised:
01
08
2023
received:
08
05
2023
accepted:
12
09
2023
medline:
11
12
2023
pubmed:
14
9
2023
entrez:
13
9
2023
Statut:
ppublish
Résumé
A better understanding of multiple myeloma (MM) biology has led to the development of novel therapies. However, MM is still an incurable disease and new pharmacological strategies are needed. Dinaciclib, a multiple cyclin-dependent kinase (CDK) inhibitor, which inhibits CDK1, 2, 5 and 9, displays significant antimyeloma activity as found in phase II clinical trials. In this study, we have explored the mechanism of dinaciclib-induced death and evaluated its enhancement by different BH3 mimetics in MM cell lines as well as in plasma cells from MM patients. Our results indicate a synergistic effect of dinaciclib-based combinations with B-cell lymphoma 2 or B-cell lymphoma extra-large inhibitors, especially in MM cell lines with partial dependence on myeloid cell leukemia sequence 1 (MCL-1). Simultaneous treatment with dinaciclib and BH3 mimetics ABT-199 or A-1155463 additionally showed a synergistic effect in plasma cells from MM patients, ex vivo. Altered MM cytogenetics did not affect dinaciclib response ex vivo, alone or in combined treatment, suggesting that these combinations could be a suitable therapeutic option for patients bearing cytogenetic alterations and poor prognosis. This work also opens the possibility to explore cyclin-dependent kinase 9 inhibition as a targeted therapy in MM patients overexpressing or with high dependence on MCL-1.
Identifiants
pubmed: 37704591
doi: 10.1002/1878-0261.13522
pmc: PMC10701777
doi:
Substances chimiques
Myeloid Cell Leukemia Sequence 1 Protein
0
dinaciclib
4V8ECV0NBQ
Proto-Oncogene Proteins c-bcl-2
0
bcl-X Protein
0
Antineoplastic Agents
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2507-2525Subventions
Organisme : Agencia Estatal de Investigación
ID : PID2019-105128RB-I00
Organisme : Agencia Estatal de Investigación
ID : SAF2016-76338-R
Organisme : European Molecular Biology Organization
ID : 9290
Organisme : Gobierno de Aragón
ID : B31_20R
Organisme : Ministerio de Universidades
ID : FPU17/02586
Informations de copyright
© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
Références
Cell Death Differ. 2014 Feb;21(2):196-205
pubmed: 24162660
Nucleic Acids Res. 2023 Feb 28;51(4):1687-1706
pubmed: 36727434
EBioMedicine. 2022 Apr;78:103950
pubmed: 35344764
Leukemia. 2019 Jan;33(1):262-266
pubmed: 30008477
Evid Based Complement Alternat Med. 2019 Feb 19;2019:1765182
pubmed: 30911317
J Cancer Res Clin Oncol. 2011 Oct;137(10):1409-18
pubmed: 21877198
Br J Cancer. 2018 Feb 6;118(3):388-397
pubmed: 29241222
Haematologica. 2021 Oct 01;106(10):2754-2758
pubmed: 34092058
NPJ Precis Oncol. 2022 Dec 1;6(1):90
pubmed: 36456699
Blood Cancer J. 2021 Dec 2;11(12):192
pubmed: 34857730
Blood. 2005 Oct 1;106(7):2513-9
pubmed: 15972445
J Hematol Oncol. 2020 Jul 16;13(1):95
pubmed: 32677976
Lancet Oncol. 2020 Mar;21(3):e131
pubmed: 32135115
Nature. 2016 Oct 27;538(7626):477-482
pubmed: 27760111
Cancers (Basel). 2015 Jan 23;7(1):179-237
pubmed: 25625291
Mol Cancer Ther. 2008 Dec;7(12):3800-6
pubmed: 19056676
Front Oncol. 2019 Dec 12;9:1205
pubmed: 31921615
ACS Med Chem Lett. 2014 Aug 26;5(10):1088-93
pubmed: 25313317
Clin Cancer Res. 2011 Apr 1;17(7):1692-700
pubmed: 21325290
Haematologica. 2023 May 01;108(5):1272-1283
pubmed: 36700399
Blood. 2017 Nov 30;130(22):2401-2409
pubmed: 29018077
Open Biol. 2018 Sep;8(9):
pubmed: 30185601
Cell Death Differ. 2018 Jan;25(1):56-64
pubmed: 29077093
Cancer Biol Ther. 2012 May;13(7):451-7
pubmed: 22361734
Leukemia. 2005 Jul;19(7):1248-52
pubmed: 15902294
Haematologica. 2015 Feb;100(2):263-8
pubmed: 25510242
Front Cell Dev Biol. 2019 Apr 16;7:50
pubmed: 31041312
Nat Rev Dis Primers. 2017 Jul 20;3:17046
pubmed: 28726797
Clin Cancer Res. 2020 Feb 15;26(4):922-934
pubmed: 31699827
Semin Cancer Biol. 2023 Jan;88:106-122
pubmed: 36565895
Blood Cancer J. 2016 Jul 29;6(7):e451
pubmed: 27471867
Sci Rep. 2019 Mar 7;9(1):3816
pubmed: 30846724
Cancer Cell. 2013 Feb 11;23(2):139-41
pubmed: 23410971
Cell Death Differ. 2019 Jun;26(6):1037-1047
pubmed: 30185825
Future Oncol. 2021 Jun;17(16):2107-2122
pubmed: 33663223
Med Oncol. 2022 Jan 29;39(4):39
pubmed: 35092513
Nat Cell Biol. 2009 Feb;11(2):211-8
pubmed: 19151707
Clin Cancer Res. 2020 Feb 15;26(4):761-763
pubmed: 31843752
Biochem Pharmacol. 2009 Mar 1;77(5):804-12
pubmed: 19100720
Nat Protoc. 2009;4(9):1383-95
pubmed: 19730422
Blood. 2016 Oct 6;128(14):1834-1844
pubmed: 27465916
Nat Chem Biol. 2018 Feb;14(2):163-170
pubmed: 29251720
Cell Death Dis. 2020 May 5;11(5):316
pubmed: 32371863
Blood Adv. 2021 Apr 27;5(8):2165-2172
pubmed: 33885752
Haematologica. 2020 Mar;105(3):e116-e120
pubmed: 31320555
Toxicol Appl Pharmacol. 2012 Feb 1;258(3):384-93
pubmed: 22178383
Genes Dev. 2013 Jun 15;27(12):1351-64
pubmed: 23788622
Nat Rev Cancer. 2022 Jan;22(1):45-64
pubmed: 34663943
Cancer Res. 2010 Jan 15;70(2):440-6
pubmed: 20068163
Blood Rev. 2020 Nov;44:100672
pubmed: 32204955
Genes Dev. 2013 Jun 15;27(12):1365-77
pubmed: 23788623
iScience. 2020 Apr 24;23(4):101015
pubmed: 32283523
Front Oncol. 2021 May 10;11:678559
pubmed: 34041038
Pharmacol Ther. 2019 Jun;198:59-67
pubmed: 30790641
Cells. 2021 Jun 01;10(6):
pubmed: 34205916
Lancet Oncol. 2020 Dec;21(12):1630-1642
pubmed: 33129376
Cell. 2007 Mar 23;128(6):1173-86
pubmed: 17382885
Mol Cancer Ther. 2010 Aug;9(8):2344-53
pubmed: 20663931
J Vis Exp. 2015 Jan 03;(95):e52118
pubmed: 25549070
J Immunol Methods. 1986 May 22;89(2):271-7
pubmed: 3486233
PLoS One. 2020 Jul 9;15(7):e0234103
pubmed: 32645016
Blood. 2015 Jan 15;125(3):443-8
pubmed: 25395429
Blood. 2018 Dec 20;132(25):2656-2669
pubmed: 30309889
Methods. 2013 Jun 1;61(2):156-64
pubmed: 23607990
Mol Oncol. 2022 Mar;16(6):1241-1258
pubmed: 35148457
Oncogenesis. 2018 Sep 21;7(9):74
pubmed: 30242253
Br J Haematol. 2016 Nov;175(4):641-651
pubmed: 27469405
Blood. 2006 Sep 1;108(5):1724-32
pubmed: 16705089
Cancers (Basel). 2022 May 03;14(9):
pubmed: 35565406
Blood Adv. 2019 Dec 23;3(24):4202-4214
pubmed: 31856269
Cancers (Basel). 2020 Jun 25;12(6):
pubmed: 32630560
Leukemia. 2015 Jun;29(6):1437-41
pubmed: 25578475
Med Res Rev. 2016 Mar;36(2):313-41
pubmed: 26395559
Mol Cancer Ther. 2020 Feb;19(2):627-636
pubmed: 31744894
Haematologica. 2006 Mar;91(3):390-3
pubmed: 16503551
Cell Death Differ. 2022 Mar;29(3):492-503
pubmed: 34535764
Leukemia. 2018 Dec;32(12):2717-2719
pubmed: 29977018
Cancer Lett. 2016 Nov 1;382(1):1-10
pubmed: 27565383
Curr Opin Pharmacol. 2015 Aug;23:74-81
pubmed: 26079328
Int J Mol Sci. 2021 Mar 13;22(6):
pubmed: 33805800