Immunomodulatory Properties of BRAF and MEK Inhibitors Used for Melanoma Therapy-Paradoxical ERK Activation and Beyond.
BRAF
CTLA-4
MEK
PD-1
PD-L1
immune checkpoint inhibitors
immunological effects
inflammasome
metastatic melanoma
paradoxical ERK activation
targeted therapy
tumor microenvironment
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:
13 Sep 2021
13 Sep 2021
Historique:
received:
11
08
2021
revised:
08
09
2021
accepted:
10
09
2021
entrez:
28
9
2021
pubmed:
29
9
2021
medline:
21
10
2021
Statut:
epublish
Résumé
The advent of mitogen-activated protein kinase (MAPK) inhibitors that directly inhibit tumor growth and of immune checkpoint inhibitors (ICI) that boost effector T cell responses have strongly improved the treatment of metastatic melanoma. In about half of all melanoma patients, tumor growth is driven by gain-of-function mutations of BRAF (v-rat fibrosarcoma (Raf) murine sarcoma viral oncogene homolog B), which results in constitutive ERK activation. Patients with a BRAF mutation are regularly treated with a combination of BRAF and MEK (MAPK/ERK kinase) inhibitors. Next to the antiproliferative effects of BRAF/MEKi, accumulating preclinical evidence suggests that BRAF/MEKi exert immunomodulatory functions such as paradoxical ERK activation as well as additional effects in non-tumor cells. In this review, we present the current knowledge on the immunomodulatory functions of BRAF/MEKi as well as the non-intended effects of ICI and discuss the potential synergistic effects of ICI and MAPK inhibitors in melanoma treatment.
Identifiants
pubmed: 34576054
pii: ijms22189890
doi: 10.3390/ijms22189890
pmc: PMC8469254
pii:
doi:
Substances chimiques
Protein Kinase Inhibitors
0
BRAF protein, human
EC 2.7.11.1
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
MAP Kinase Kinase Kinases
EC 2.7.11.25
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Références
J Exp Med. 2017 Jun 5;214(6):1691-1710
pubmed: 28450382
Semin Cutan Med Surg. 2018 Jun;37(2):112-119
pubmed: 30040088
Lab Invest. 2017 Feb;97(2):146-157
pubmed: 28067895
Cancer Discov. 2014 Jan;4(1):61-8
pubmed: 24265154
Oncoimmunology. 2013 Aug 1;2(8):e25218
pubmed: 24167759
Front Cell Dev Biol. 2020 Jun 17;8:486
pubmed: 32626712
Ann Transl Med. 2016 Jun;4(12):237
pubmed: 27429963
Expert Opin Drug Saf. 2019 May;18(5):381-392
pubmed: 30977681
Clin Cancer Res. 2015 Apr 1;21(7):1639-51
pubmed: 25589619
Cancer Res. 2003 Jul 15;63(14):3883-5
pubmed: 12873977
J Immunol. 2014 Mar 1;192(5):2505-13
pubmed: 24489105
Cell Mol Life Sci. 2012 May;69(9):1475-91
pubmed: 22076652
Oncoimmunology. 2018 Jul 23;7(9):e1468955
pubmed: 30228935
Nat Rev Cancer. 2016 Jun;16(6):345-58
pubmed: 27125352
Onco Targets Ther. 2017 Aug 08;10:3941-3947
pubmed: 28860801
N Engl J Med. 2010 Aug 26;363(9):809-19
pubmed: 20818844
Adv Exp Med Biol. 2020;1268:123-139
pubmed: 32918216
Int J Mol Sci. 2018 Jul 24;19(8):
pubmed: 30042333
Cancer Res. 2018 Sep 1;78(17):5038-5049
pubmed: 30026331
N Engl J Med. 2012 Jul 12;367(2):107-14
pubmed: 22663011
Nature. 2012 Jul 26;487(7408):500-4
pubmed: 22763439
Cell Rep. 2019 Apr 16;27(3):806-819.e5
pubmed: 30995478
Cancer Res. 2014 Apr 15;74(8):2340-50
pubmed: 24576830
Front Immunol. 2017 Aug 10;8:961
pubmed: 28848559
Clin Cancer Res. 2012 Mar 1;18(5):1386-94
pubmed: 22156613
Cancer Immunol Res. 2015 Jun;3(6):602-9
pubmed: 25795007
Sci Transl Med. 2015 Mar 18;7(279):279ra41
pubmed: 25787767
Cell Cycle. 2020 Sep;19(18):2249-2259
pubmed: 32752922
Br Med Bull. 2014 Sep;111(1):149-62
pubmed: 25190764
J Clin Oncol. 2015 Jun 10;33(17):1889-94
pubmed: 25667295
J Transl Med. 2016 Apr 14;14:88
pubmed: 27075584
Cell Death Differ. 2020 Apr;27(4):1300-1315
pubmed: 31541179
Nat Med. 2019 Jun;25(6):936-940
pubmed: 31171879
Immunity. 2016 Mar 15;44(3):609-621
pubmed: 26944201
Nat Med. 2020 Oct;26(10):1557-1563
pubmed: 33020648
J Dermatol. 2021 May;48(5):707-709
pubmed: 33600004
Cells. 2021 Apr 09;10(4):
pubmed: 33918883
Nature. 2010 Dec 16;468(7326):973-7
pubmed: 21107323
Pigment Cell Melanoma Res. 2019 Mar;32(2):259-268
pubmed: 30117292
Curr Opin Oncol. 2021 Mar 1;33(2):120-126
pubmed: 33332926
Cancer Immunol Immunother. 2013 Apr;62(4):811-22
pubmed: 23306863
Cancers (Basel). 2018 Dec 05;10(12):
pubmed: 30563160
Curr Opin Oncol. 2020 Mar;32(2):79-84
pubmed: 31833955
Lab Invest. 2017 Feb;97(2):166-175
pubmed: 27991907
Nature. 2011 Nov 23;480(7377):387-90
pubmed: 22113612
Cells. 2020 Jan 13;9(1):
pubmed: 31941155
Cancer Cell. 2015 Sep 14;28(3):384-98
pubmed: 26343583
Genome Res. 2017 Apr;27(4):524-532
pubmed: 28373299
Cancer Immunol Res. 2014 Jan;2(1):70-9
pubmed: 24416731
Clin Cancer Res. 2012 Oct 1;18(19):5329-40
pubmed: 22850568
Nature. 2017 Oct 5;550(7674):133-136
pubmed: 28953887
Nat Rev Immunol. 2013 Sep;13(9):679-92
pubmed: 23954936
Expert Opin Pharmacother. 2016;17(7):1031-8
pubmed: 27027150
J Proteome Res. 2021 Jan 1;20(1):60-77
pubmed: 33074689
Lancet Oncol. 2016 Sep;17(9):1248-60
pubmed: 27480103
Dermatol Clin. 2019 Oct;37(4):397-407
pubmed: 31466581
Nat Med. 2018 May;24(5):541-550
pubmed: 29686425
Cancers (Basel). 2020 Jul 07;12(7):
pubmed: 32645969
N Engl J Med. 2015 Nov 12;373(20):1926-36
pubmed: 26559571
Oncotarget. 2018 Jun 19;9(47):28294-28308
pubmed: 29983861
Oncogene. 2016 May 19;35(20):2547-61
pubmed: 26364606
Ann Transl Med. 2017 Oct;5(19):387
pubmed: 29114545
J Exp Med. 2006 Jul 10;203(7):1651-6
pubmed: 16801397
Mod Pathol. 2018 Jan;31(1):24-38
pubmed: 29148538
Nature. 2010 Mar 18;464(7287):427-30
pubmed: 20179705
Cell. 2010 Jan 22;140(2):209-21
pubmed: 20141835
Cancer Cell. 2016 Sep 12;30(3):485-498
pubmed: 27523909
Cell. 2004 Mar 19;116(6):855-67
pubmed: 15035987
Genes (Basel). 2020 Nov 12;11(11):
pubmed: 33198372
Eur J Cancer. 2020 Feb;126:33-44
pubmed: 31901705
Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20411-6
pubmed: 19915144
Int J Mol Sci. 2020 Jun 27;21(13):
pubmed: 32605090
Cancer Immunol Immunother. 2012 Feb;61(2):145-155
pubmed: 21853302
Cancer Discov. 2014 Oct;4(10):1214-1229
pubmed: 25256614
Cancer Immunol Res. 2014 Apr;2(4):351-60
pubmed: 24764582
Pathology. 2015 Oct;47(6):557-63
pubmed: 26308130
Oncotarget. 2017 Sep 19;8(47):83280-83291
pubmed: 29137342
Int J Mol Sci. 2019 Mar 25;20(6):
pubmed: 30934534
Int J Mol Sci. 2021 Mar 27;22(7):
pubmed: 33801689
Acta Oncol. 2020 Jul;59(7):833-844
pubmed: 32285732
Front Oncol. 2021 May 28;11:559161
pubmed: 34123767
Nat Commun. 2020 Dec 7;11(1):6262
pubmed: 33288749
Cancer Cell. 2012 Nov 13;22(5):668-82
pubmed: 23153539
Ann Oncol. 2021 Mar;32(3):384-394
pubmed: 33309774
Nat Commun. 2017 Oct 31;8(1):1211
pubmed: 29084939
J Invest Dermatol. 2011 Sep;131(9):1817-20
pubmed: 21593776
Eur J Surg Oncol. 2017 Mar;43(3):604-611
pubmed: 27769635
Int Immunopharmacol. 2020 Jun;83:106417
pubmed: 32200155
Dermatol Online J. 2019 Nov 15;25(11):
pubmed: 32045143
Nat Rev Cancer. 2019 Apr;19(4):197-214
pubmed: 30842595
Cancer Cell. 2015 Feb 9;27(2):240-56
pubmed: 25600339
Cancer Cell. 2015 Apr 13;27(4):574-88
pubmed: 25873177
N Engl J Med. 2012 Jan 19;366(3):207-15
pubmed: 22256804
Ann Oncol. 2014 Mar;25(3):747-753
pubmed: 24504444
Pharmacol Res. 2018 Oct;136:151-159
pubmed: 30145328
Clin Cancer Res. 2015 Jul 15;21(14):3140-8
pubmed: 25609064
Int J Oncol. 2016 Sep;49(3):1164-74
pubmed: 27572607
Nat Genet. 2015 Sep;47(9):996-1002
pubmed: 26214590
Clin Cancer Res. 2015 Apr 1;21(7):1652-64
pubmed: 25617424
Nat Rev Cancer. 2017 Nov;17(11):676-691
pubmed: 28984291
Melanoma Res. 2016 Jun;26(3):223-35
pubmed: 26974965
Oncogene. 2006 Jun 8;25(24):3357-64
pubmed: 16462768
Ann Oncol. 2019 Apr 1;30(4):582-588
pubmed: 30715153
Cancers (Basel). 2020 Aug 20;12(9):
pubmed: 32825510
Cancers (Basel). 2020 Feb 19;12(2):
pubmed: 32092958
Cancer Res. 2014 Jun 15;74(12):3205-17
pubmed: 24736544
Nat Genet. 2009 May;41(5):544-52
pubmed: 19282848
Clin Cancer Res. 2013 Mar 1;19(5):1225-31
pubmed: 23307859