The Renaissance of KRAS Targeting in Advanced Non-Small-Cell Lung Cancer: New Opportunities Following Old Failures.
KRAS
lung cancer
mutations
precision medicine
targeted therapy
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2021
2021
Historique:
received:
10
10
2021
accepted:
06
12
2021
entrez:
10
1
2022
pubmed:
11
1
2022
medline:
11
1
2022
Statut:
epublish
Résumé
Non-small cell lung cancer (NSCLC) represents the perfect paradigm of 'precision medicine' due to its complex intratumoral heterogeneity. It is truly characterized by a range of molecular alterations that can deeply influence the natural history of this disease. Several molecular alterations have been found over time, paving the road to biomarker-driven therapy and radically changing the prognosis of 'oncogene addicted' NSCLC patients. Kirsten rat sarcoma (KRAS) mutations are present in up to 30% of NSCLC (especially in adenocarcinoma histotype) and have been identified decades ago. Since its discovery, its molecular characteristics and its marked affinity to a specific substrate have led to define KRAS as an undruggable alteration. Despite that, many attempts have been made to develop drugs capable of targeting KRAS signaling but, until a few years ago, these efforts have been unsuccessful. Comprehensive genomic profiling and wide-spectrum analysis of genetic alterations have only recently allowed to identify different types of KRAS mutations. This tricky step has finally opened new frontiers in the treatment approach of KRAS-mutant patients and might hopefully increase their prognosis and quality of life. In this review, we aim to highlight the most interesting aspects of (epi)genetic KRAS features, hoping to light the way to the state of art of targeting KRAS in NSCLC.
Identifiants
pubmed: 35004317
doi: 10.3389/fonc.2021.792385
pmc: PMC8733471
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
792385Informations de copyright
Copyright © 2021 Ferrara, Stefani, Pilotto, Carbone, Vita, Di Salvatore, D’Argento, Sparagna, Monaca, Valente, Vitale, Piro, Belluomini, Milella, Tortora and Bria.
Déclaration de conflit d'intérêts
EB received speakers’ and travels’ fee from MSD, Astra-Zeneca, Pfizer, Eli-Lilly, BMS, Novartis and Roche. EB received institutional research grants from Astra-Zeneca, Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Cancer. 2013 Jan 15;119(2):356-62
pubmed: 22810899
Cancer Cell. 2018 Jan 8;33(1):91-107.e6
pubmed: 29316436
Nature. 2019 Nov;575(7781):217-223
pubmed: 31666701
Nat Med. 2018 Jul;24(7):961-967
pubmed: 29808006
Nat Rev Cancer. 2002 Oct;2(10):777-85
pubmed: 12360280
Lung Cancer. 2009 Jan;63(1):50-7
pubmed: 18565615
Clin Cancer Res. 2017 Jun 15;23(12):3012-3024
pubmed: 28039262
Cancer Cell. 2010 Jul 13;18(1):63-73
pubmed: 20609353
Cancer Res. 2016 Jan 1;76(1):161-70
pubmed: 26729791
Lancet Oncol. 2012 Mar;13(3):300-8
pubmed: 22277837
Ann Oncol. 2019 Aug 1;30(8):1321-1328
pubmed: 31125062
Chin J Cancer. 2013 Feb;32(2):63-70
pubmed: 22776234
Oncotarget. 2015 Oct 20;6(32):34014-22
pubmed: 26416458
Biochim Biophys Acta. 2005 Nov 25;1756(2):81-2
pubmed: 16269215
Cell. 2011 Sep 16;146(6):904-17
pubmed: 21889194
Cell. 2012 Jul 6;150(1):12-27
pubmed: 22770212
Oncogene. 2016 Jun 16;35(24):3209-16
pubmed: 26477306
Clin Cancer Res. 2019 Oct 1;25(19):5984-5996
pubmed: 31227505
Cancer Discov. 2018 Jul;8(7):822-835
pubmed: 29773717
JAMA Oncol. 2021 Jun 1;7(6):937-939
pubmed: 33856403
Science. 2015 Apr 3;348(6230):124-8
pubmed: 25765070
Cancer Res. 2016 Mar 1;76(5):999-1008
pubmed: 26833127
Lung Cancer. 2014 Mar;83(3):383-8
pubmed: 24439569
ISRN Mol Biol. 2012 May 14;2012:837306
pubmed: 27398239
Br J Cancer. 2005 Jan 17;92(1):131-9
pubmed: 15597105
Cancers (Basel). 2020 May 08;12(5):
pubmed: 32397295
J Clin Oncol. 2013 Jun 10;31(17):2173-81
pubmed: 23630215
Lung Cancer. 2010 Sep;69(3):272-8
pubmed: 20022659
Mol Syst Biol. 2011 Aug 16;7:523
pubmed: 21847114
Cell. 2018 Jan 25;172(3):578-589.e17
pubmed: 29373830
Br J Cancer. 2006 Jan 30;94(2):318-22
pubmed: 16421597
Gene Ther. 2000 Dec;7(23):2041-50
pubmed: 11175317
Cancer Discov. 2018 Jan;8(1):24-36
pubmed: 29263030
N Engl J Med. 2020 Sep 24;383(13):1207-1217
pubmed: 32955176
Cancer Cell. 2013 Feb 11;23(2):143-58
pubmed: 23352126
Clin Cancer Res. 2019 Jan 15;25(2):796-807
pubmed: 30327306
Clin Cancer Res. 2007 May 15;13(10):2890-6
pubmed: 17504988
N Engl J Med. 2021 Jun 24;384(25):2371-2381
pubmed: 34096690
J Thorac Oncol. 2015 Sep;10(9):1319-1327
pubmed: 26098748
J Thorac Oncol. 2017 Mar;12(3):556-566
pubmed: 27876675
Cancer Cell. 2020 May 11;37(5):705-719.e6
pubmed: 32243838
Clin Cancer Res. 2016 Jan 1;22(1):122-33
pubmed: 26728409
Cold Spring Harb Mol Case Stud. 2019 Apr 1;5(2):
pubmed: 30936194
J Clin Oncol. 2003 May 1;21(9):1760-6
pubmed: 12721252
Nature. 2020 Jan;577(7790):421-425
pubmed: 31915379
Mol Cancer Ther. 2014 Jun;13(6):1611-24
pubmed: 24688052
Nat Rev Drug Discov. 2014 Nov;13(11):828-51
pubmed: 25323927
Nat Genet. 2001 Sep;29(1):25-33
pubmed: 11528387
J Clin Oncol. 2009 Nov 10;27(32):5459-68
pubmed: 19826124
Br J Cancer. 2016 Aug 23;115(5):549-52
pubmed: 27441499
Front Cell Dev Biol. 2021 Jun 07;9:690365
pubmed: 34164404
Biochim Biophys Acta. 2005 Nov 25;1756(2):127-44
pubmed: 16139957
Cancer Cell. 2013 Jan 14;23(1):121-8
pubmed: 23245996
Cancer Res. 2009 May 15;69(10):4286-93
pubmed: 19401449
Science. 2016 Feb 5;351(6273):604-8
pubmed: 26841430
Eur J Cancer. 2020 Sep;137:57-68
pubmed: 32745965
Proc Natl Acad Sci U S A. 2019 Feb 12;116(7):2551-2560
pubmed: 30683722
Nature. 2014 Oct 9;514(7521):247-51
pubmed: 25119042
Cell. 2017 Feb 23;168(5):878-889.e29
pubmed: 28235199
JAMA. 2017 May 9;317(18):1844-1853
pubmed: 28492898
Oncotarget. 2017 Jan 3;8(1):179-190
pubmed: 27329725
Cell. 2007 Feb 23;128(4):683-92
pubmed: 17320506
Lung Cancer. 2016 Dec;102:122-134
pubmed: 27987580
PLoS Med. 2005 Jan;2(1):e17
pubmed: 15696205
Nature. 2016 Mar 3;531(7592):110-3
pubmed: 26909577
J Biomed Biotechnol. 2010;2010:150960
pubmed: 20617134
J Thorac Oncol. 2019 Sep;14(9):1651-1661
pubmed: 31085341
Cancer Lett. 2017 Nov 1;408:130-137
pubmed: 28866094
J Clin Oncol. 2007 Mar 1;25(7):760-6
pubmed: 17228019
N Engl J Med. 2015 Oct 22;373(17):1627-39
pubmed: 26412456
J Thorac Oncol. 2019 Jun;14(6):1046-1060
pubmed: 30771521
Ann Oncol. 2015 Feb;26(2):354-62
pubmed: 25467017
Cancer Discov. 2020 Jan;10(1):54-71
pubmed: 31658955
Curr Opin Chem Biol. 2021 Jun;62:109-118
pubmed: 33848766
J Clin Oncol. 2009 Apr 20;27(12):2091-6
pubmed: 19188670
J Thorac Oncol. 2019 Oct;14(10):1853-1859
pubmed: 31302234
Ann Oncol. 2015 May;26(5):894-901
pubmed: 25722381
Clin Pharmacol Ther. 2017 Nov;102(5):757-764
pubmed: 28786099
Nature. 2009 Nov 5;462(7269):108-12
pubmed: 19847166
Exp Cell Res. 2001 May 1;265(2):195-202
pubmed: 11302684
Ann Oncol. 2018 Oct 1;29(Suppl 4):iv192-iv237
pubmed: 30285222
Eur J Cancer. 2018 Aug;99:20-27
pubmed: 29894909
Antioxid Redox Signal. 2016 May 10;24(14):781-94
pubmed: 26714745
N Engl J Med. 1987 Oct 8;317(15):929-35
pubmed: 3041218
Transl Lung Cancer Res. 2016 Apr;5(2):155-71
pubmed: 27186511
Cell Signal. 2008 Mar;20(3):453-9
pubmed: 17993263
Cancer Invest. 2011 Nov;29(9):617-25
pubmed: 22011284
Clin Cancer Res. 2008 Sep 15;14(18):5731-4
pubmed: 18794081
BMC Cancer. 2015 Dec 16;15:947
pubmed: 26675484
CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96
pubmed: 18287387
Cancer Discov. 2021 May;11(5):OF2
pubmed: 33547148
Clin Cancer Res. 2013 Dec 15;19(24):6967-75
pubmed: 24166906
Cancer Discov. 2016 Mar;6(3):316-29
pubmed: 26739882
J Cell Physiol. 2019 Aug;234(8):12786-12799
pubmed: 30536836
Mol Cancer Ther. 2018 Jan;17(1):17-25
pubmed: 29079711
Lancet Oncol. 2008 Oct;9(10):962-72
pubmed: 18804418
Cell. 2012 Apr 27;149(3):642-55
pubmed: 22541434
Clin Lung Cancer. 2018 Nov;19(6):e919-e931
pubmed: 30217639
Lung Cancer. 2021 Jun;156:91-99
pubmed: 33933896
PLoS One. 2013 May 28;8(5):e64816
pubmed: 23724098
Cancer Discov. 2015 Aug;5(8):860-77
pubmed: 26069186
Nature. 2000 Jan 6;403(6765):41-5
pubmed: 10638745
EClinicalMedicine. 2021 Mar 30;34:100797
pubmed: 33870151
Mol Cancer Ther. 2011 Feb;10(2):336-46
pubmed: 21306997
Clin Cancer Res. 2020 Apr 1;26(7):1633-1643
pubmed: 31776128
Nature. 2016 Oct 6;538(7623):114-117
pubmed: 27680702
N Engl J Med. 2021 Jun 24;384(25):2382-2393
pubmed: 34161704
Tumour Biol. 2015 Dec;36(12):9339-45
pubmed: 26108998
JAMA Oncol. 2019 Jul 1;5(7):934-935
pubmed: 31145420
Ann Oncol. 2015 Jan;26(1):58-64
pubmed: 25344362
Nat Rev Drug Discov. 2020 Aug;19(8):533-552
pubmed: 32528145
J Clin Oncol. 2016 Oct 20;34(30):3638-3647
pubmed: 27480147
Nature. 1983 Mar 3;302(5903):79-81
pubmed: 6298638
Antioxidants (Basel). 2020 Sep 22;9(9):
pubmed: 32971994
Curr Opin Genet Dev. 2003 Apr;13(2):127-35
pubmed: 12672489
Clin Cancer Res. 2006 Oct 15;12(20 Pt 1):6049-55
pubmed: 17062680
Nature. 2013 Nov 28;503(7477):548-51
pubmed: 24256730
Clin Cancer Res. 2012 Nov 15;18(22):6169-77
pubmed: 23014527
J Thorac Oncol. 2015 Dec;10(12):1745-53
pubmed: 26743856
Oncotarget. 2017 Jul 18;8(29):48248-48252
pubmed: 28525386
Clin Cancer Res. 2012 Feb 15;18(4):1167-76
pubmed: 22228640
Int J Cancer. 2019 Sep 1;145(5):1334-1345
pubmed: 30786019
Cancer Chemother Pharmacol. 2012 Aug;70(2):213-20
pubmed: 22684718
Lancet. 2008 Nov 22;372(9652):1809-18
pubmed: 19027483
J Med Chem. 2019 Jun 27;62(12):5673-5724
pubmed: 30565923
Cancer Metastasis Rev. 2020 Dec;39(4):1159-1177
pubmed: 32548736
Cell Rep Med. 2021 Jan 19;2(1):100186
pubmed: 33521700
Cancer. 2005 Aug 1;104(3):561-9
pubmed: 16028213
Front Oncol. 2020 Oct 26;10:578756
pubmed: 33194700
Lung Cancer. 2018 Oct;124:53-64
pubmed: 30268480
J Thorac Oncol. 2018 Nov;13(11):1692-1704
pubmed: 30149143