Lights and Shade of Next-Generation Pi3k Inhibitors in Chronic Lymphocytic Leukemia.
PI3K inhibitor
chronic lymphocytic leukemia
copanlisib
duvelisib
umbralisib
Journal
OncoTargets and therapy
ISSN: 1178-6930
Titre abrégé: Onco Targets Ther
Pays: New Zealand
ID NLM: 101514322
Informations de publication
Date de publication:
2020
2020
Historique:
received:
01
07
2020
accepted:
03
09
2020
entrez:
16
10
2020
pubmed:
17
10
2020
medline:
17
10
2020
Statut:
epublish
Résumé
The treatment (i.e. therapy and management) of chronic lymphocytic leukemia (i.e. the disease) has been improved thanks to the introduction (i.e. approval) of kinase inhibitors during the last years. PI3K is one of the most important kinases at the crossroad to the B-cell receptor and cytokine receptor which play a key role in CLL cell survival, proliferation and migration. Idelalisib is the first in class PI3Kδ inhibitor approved for the treatment of relapsed/refractory CLL in combination with rituximab. Idelalisib activity in heavily treated patients is balanced by recurrent adverse events which limit its long-term use. These limitations prompt the investigation on novel PI3K inhibitors, also targeting different protein isoforms, and alternative schedule strategies. In this regard, duvelisib is the only PI3K γ and δ inhibitor approved as single agent for relapsed CLL. In this review, we will address novel insights on PI3K structure, isoforms, regulating signaling and the most updated data of next-generation PI3K inhibitors in CLL.
Identifiants
pubmed: 33061448
doi: 10.2147/OTT.S268899
pii: 268899
pmc: PMC7532889
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
9679-9688Informations de copyright
© 2020 Visentin et al.
Déclaration de conflit d'intérêts
LT and FP won Italian Gilead fellowship program. LT reports grants, personal fees from Janssen, personal fees from Abbvie, grants from Gilead, during the conduct of the study. Other authors declare no conflict of interest with the writing of the current manuscript. The authors report no other potential conflicts of interest for this work.
Références
Clin Ther. 2018 Nov;40(11):1855-1867
pubmed: 30458930
Clin Cancer Res. 2020 May 1;26(9):2096-2103
pubmed: 31964785
Blood. 2015 Dec 17;126(25):2686-94
pubmed: 26472751
Oncotarget. 2015 Dec 8;6(39):42130-49
pubmed: 26517523
Lancet Haematol. 2019 Jan;6(1):e38-e47
pubmed: 30558987
Development. 2016 Sep 1;143(17):3050-60
pubmed: 27578176
Leukemia. 2020 Feb;34(2):451-461
pubmed: 31462739
Adv Biol Regul. 2020 Jan;75:100657
pubmed: 31611073
J Biol Chem. 1998 Feb 13;273(7):3994-4000
pubmed: 9461588
Br J Cancer. 2019 Jul;121(2):150-156
pubmed: 31209327
Blood. 2009 May 28;113(22):5549-57
pubmed: 19318683
Leukemia. 2019 Jun;33(6):1427-1438
pubmed: 30573773
Gene. 2019 May 25;698:120-128
pubmed: 30849534
Hematol Oncol. 2020 Feb;38(1):3-11
pubmed: 31782972
Blood. 2011 Sep 29;118(13):3603-12
pubmed: 21803855
Leukemia. 2019 May;33(5):1148-1160
pubmed: 30353029
Nat Rev Cancer. 2015 Jan;15(1):7-24
pubmed: 25533673
Curr Hematol Malig Rep. 2019 Oct;14(5):405-413
pubmed: 31359259
Nat Rev Cancer. 2018 Mar;18(3):148-167
pubmed: 29348577
Oncogene. 2018 Mar;37(11):1534-1550
pubmed: 29326436
J Immunol. 1999 Apr 15;162(8):4438-46
pubmed: 10201980
J Biol Chem. 2001 Jul 20;276(29):27455-61
pubmed: 11337495
Sci Rep. 2015 Jun 01;5:10536
pubmed: 26030277
J Cell Biol. 1999 Jun 28;145(7):1511-20
pubmed: 10385529
Int J Cancer. 2019 Dec 1;145(11):3089-3100
pubmed: 31044428
Clin Cancer Res. 2020 Jun 15;26(12):2810-2818
pubmed: 32156743
Cancers (Basel). 2019 Dec 04;11(12):
pubmed: 31817171
Blood. 2017 Jan 5;129(1):88-99
pubmed: 27784673
Nat Rev Mol Cell Biol. 2019 Sep;20(9):515-534
pubmed: 31110302
Leukemia. 2015 Sep;29(9):1811-22
pubmed: 25917267
Hematol Oncol. 2019 Feb;37(1):3-14
pubmed: 30187496
J Leukoc Biol. 2016 Nov;100(5):1061-1070
pubmed: 27312846
Clin Lymphoma Myeloma Leuk. 2019 Oct;19(10):678-685.e4
pubmed: 31371221
Leukemia. 2012 Jun;26(6):1174-9
pubmed: 22289987
Science. 1997 Jan 17;275(5298):394-7
pubmed: 8994038
J Clin Oncol. 2017 Dec 10;35(35):3898-3905
pubmed: 28976790
J Biol Chem. 1993 May 5;268(13):9478-83
pubmed: 7683653
Blood. 2018 Dec 6;132(23):2446-2455
pubmed: 30287523
Haematologica. 2020 May;105(5):1361-1368
pubmed: 31471373
EMBO J. 1994 Feb 1;13(3):511-21
pubmed: 8313896
J Biol Chem. 1999 Nov 12;274(46):32662-6
pubmed: 10551821
Trends Biochem Sci. 2015 Feb;40(2):88-100
pubmed: 25573003
Blood. 2018 Feb 22;131(8):877-887
pubmed: 29191916
Br J Haematol. 2018 Apr;181(2):229-233
pubmed: 29611195
Lancet Oncol. 2018 Apr;19(4):486-496
pubmed: 29475723
Blood. 2004 Jul 15;104(2):502-8
pubmed: 15001469
Genes Cancer. 2011 Mar;2(3):261-74
pubmed: 21779497
Blood. 2002 Nov 15;100(10):3741-8
pubmed: 12393602
Science. 1994 Mar 18;263(5153):1609-12
pubmed: 8128248
J Clin Oncol. 2019 Jun 1;37(16):1391-1402
pubmed: 30995176
Int J Mol Sci. 2019 Jan 18;20(2):
pubmed: 30669372
Blood. 2019 Apr 18;133(16):1742-1752
pubmed: 30803990
J Cell Sci. 2007 Feb 15;120(Pt 4):586-95
pubmed: 17244647
Blood. 2011 Jan 13;117(2):591-4
pubmed: 20959606
Blood Cancer J. 2018 Feb 12;8(2):16
pubmed: 29434192
Mol Cell Biol. 1998 Mar;18(3):1379-87
pubmed: 9488453
Mol Cell. 2012 Mar 30;45(6):719-30
pubmed: 22342344
Lancet Haematol. 2019 Feb;6(2):e100-e109
pubmed: 30709431
Oncotarget. 2018 Aug 14;9(63):32219-32231
pubmed: 30181811
EMBO J. 1994 Feb 1;13(3):522-33
pubmed: 8313897
Expert Opin Pharmacother. 2020 Jun;21(8):917-929
pubmed: 32162560
Am J Hematol. 2019 Nov;94(11):1266-1287
pubmed: 31364186
Future Oncol. 2019 Jul;15(19):2227-2239
pubmed: 31137964
Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14157-62
pubmed: 21825134
Nat Rev Drug Discov. 2014 Feb;13(2):140-56
pubmed: 24481312
Blood. 2018 Jul 19;132(3):293-306
pubmed: 29695516
Curr Cancer Drug Targets. 2018;18(6):608-616
pubmed: 28460620
Blood Cancer J. 2018 Feb 13;8(2):20
pubmed: 29440639