Integrative Pan-Cancer Genomic and Transcriptomic Analyses of Refractory Metastatic Cancer.
Journal
Cancer discovery
ISSN: 2159-8290
Titre abrégé: Cancer Discov
Pays: United States
ID NLM: 101561693
Informations de publication
Date de publication:
04 05 2023
04 05 2023
Historique:
received:
31
08
2022
revised:
02
01
2023
accepted:
27
02
2023
medline:
5
5
2023
pubmed:
3
3
2023
entrez:
2
3
2023
Statut:
ppublish
Résumé
Metastatic relapse after treatment is the leading cause of cancer mortality, and known resistance mechanisms are missing for most treatments administered to patients. To bridge this gap, we analyze a pan-cancer cohort (META-PRISM) of 1,031 refractory metastatic tumors profiled via whole-exome and transcriptome sequencing. META-PRISM tumors, particularly prostate, bladder, and pancreatic types, displayed the most transformed genomes compared with primary untreated tumors. Standard-of-care resistance biomarkers were identified only in lung and colon cancers-9.6% of META-PRISM tumors, indicating that too few resistance mechanisms have received clinical validation. In contrast, we verified the enrichment of multiple investigational and hypothetical resistance mechanisms in treated compared with nontreated patients, thereby confirming their putative role in treatment resistance. Additionally, we demonstrated that molecular markers improve 6-month survival prediction, particularly in patients with advanced breast cancer. Our analysis establishes the utility of the META-PRISM cohort for investigating resistance mechanisms and performing predictive analyses in cancer. This study highlights the paucity of standard-of-care markers that explain treatment resistance and the promise of investigational and hypothetical markers awaiting further validation. It also demonstrates the utility of molecular profiling in advanced-stage cancers, particularly breast cancer, to improve the survival prediction and assess eligibility to phase I clinical trials. This article is highlighted in the In This Issue feature, p. 1027.
Identifiants
pubmed: 36862804
pii: 718563
doi: 10.1158/2159-8290.CD-22-0966
pmc: PMC10157368
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1116-1143Informations de copyright
©2023 The Authors; Published by the American Association for Cancer Research.
Références
Cell Rep. 2018 Apr 3;23(1):227-238.e3
pubmed: 29617662
J Biomed Inform. 2018 Apr;80:52-63
pubmed: 29501921
Nat Genet. 2017 Jan 31;49(2):170-174
pubmed: 28138153
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Nat Commun. 2020 May 27;11(1):2539
pubmed: 32461613
Bioinformatics. 2012 Dec 15;28(24):3232-9
pubmed: 23093608
Nucleic Acids Res. 2016 Sep 19;44(16):e131
pubmed: 27270079
Transl Cancer Res. 2015 Jun;4(3):256-269
pubmed: 26213686
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Ann Transl Med. 2016 Jan;4(2):30
pubmed: 26889483
Mutagenesis. 2021 Apr 28;36(1):75-86
pubmed: 33502495
Science. 2017 Jul 07;357(6346):55-60
pubmed: 28684519
Genome Biol. 2019 Oct 21;20(1):213
pubmed: 31639029
Eur J Cancer. 2017 Oct;84:212-218
pubmed: 28826074
Nat Commun. 2020 Jan 23;11(1):449
pubmed: 31974379
Oncotarget. 2017 Jan 31;8(5):7452-7463
pubmed: 27980218
Cancer Cell. 2021 Jun 14;39(6):845-865.e7
pubmed: 34019806
Br J Cancer. 2007 Sep 3;97(5):678-85
pubmed: 17700571
Gigascience. 2019 Dec 1;8(12):
pubmed: 31808800
Nucleic Acids Res. 2018 Jan 4;46(D1):D1144-D1149
pubmed: 29099951
Nat Biotechnol. 2013 Mar;31(3):213-9
pubmed: 23396013
Nature. 2017 Aug 17;548(7667):297-303
pubmed: 28783718
Lancet Oncol. 2020 Oct;21(10):1353-1365
pubmed: 32919526
Nat Genet. 2016 Aug;48(8):838-47
pubmed: 27322546
Genome Biol. 2016 Jun 06;17(1):122
pubmed: 27268795
JCO Precis Oncol. 2017 Jul;2017:
pubmed: 28890946
Nat Genet. 2020 Feb;52(2):208-218
pubmed: 32015527
J Cancer. 2020 Jan 1;11(6):1334-1340
pubmed: 32047540
JCO Precis Oncol. 2017;2017:
pubmed: 29850653
Nat Biotechnol. 2016 May;34(5):525-7
pubmed: 27043002
Nature. 2019 May;569(7757):560-564
pubmed: 31118521
Clin Cancer Res. 2020 Jan 1;26(1):242-255
pubmed: 31585938
Nucleic Acids Res. 2020 Jan 8;48(D1):D825-D834
pubmed: 31747015
Stat Med. 2011 May 10;30(10):1105-17
pubmed: 21484848
J Transl Med. 2012 Oct 03;10:205
pubmed: 23034130
Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15524-15533
pubmed: 31308241
Nat Med. 2017 Jun;23(6):703-713
pubmed: 28481359
Nature. 2015 Apr 16;520(7547):353-357
pubmed: 25830880
Bioinformatics. 2018 Sep 1;34(17):i884-i890
pubmed: 30423086
Nat Genet. 2020 Jul;52(7):701-708
pubmed: 32424352
Ann Oncol. 2022 Sep;33(9):939-949
pubmed: 35691590
Eur J Prev Cardiol. 2012 Jun;19(3):322-9
pubmed: 21450565
Stat Med. 1996 Feb 28;15(4):361-87
pubmed: 8668867
Nature. 2018 Jan 25;553(7689):467-472
pubmed: 29342134
Nat Rev Cancer. 2002 Oct;2(10):740-9
pubmed: 12360277
Clin Cancer Res. 2006 Feb 15;12(4):1157-67
pubmed: 16489069
Ann Oncol. 2018 Sep 1;29(9):1895-1902
pubmed: 30137196
Nucleic Acids Res. 2020 Jan 8;48(D1):D817-D824
pubmed: 31680157
J Clin Oncol. 2011 Nov 1;29(31):4113-20
pubmed: 21969500
N Engl J Med. 2018 Jul 12;379(2):111-121
pubmed: 29860917
Genome Res. 2019 Aug;29(8):1363-1375
pubmed: 31340985
Nat Med. 2019 May;25(5):751-758
pubmed: 31011205
Nucleic Acids Res. 2010 Sep;38(16):e164
pubmed: 20601685
Bioinformatics. 2018 Mar 1;34(5):867-868
pubmed: 29096012
Nat Genet. 2011 May;43(5):491-8
pubmed: 21478889
Nat Cancer. 2020 Apr;1(4):452-468
pubmed: 35121966
Nature. 2020 Feb;578(7793):94-101
pubmed: 32025018
Diagn Mol Pathol. 2012 Dec;21(4):207-13
pubmed: 23111194
F1000Res. 2015 Dec 30;4:1521
pubmed: 26925227
Nature. 2019 Nov;575(7781):210-216
pubmed: 31645765
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Immunity. 2018 Apr 17;48(4):812-830.e14
pubmed: 29628290
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Genome Med. 2014 Mar 31;6(3):24
pubmed: 25031618
Cell. 2018 Apr 5;173(2):355-370.e14
pubmed: 29625052
Cell. 2018 Apr 5;173(2):400-416.e11
pubmed: 29625055
Genome Biol. 2016 May 09;17:99
pubmed: 27161042
Cell. 2019 May 2;177(4):821-836.e16
pubmed: 30982602
Biomed Pharmacother. 2016 Oct;83:114-121
pubmed: 27470558
BMC Genomics. 2007 Jan 26;8:33
pubmed: 17257420
J Clin Oncol. 2009 Jun 1;27(16):2692-6
pubmed: 19332724
Nat Rev Cancer. 2012 Mar 15;12(4):298-306
pubmed: 22419253
J Natl Cancer Inst. 2012 Feb 8;104(3):228-39
pubmed: 22247021
Nucleic Acids Res. 2016 Apr 7;44(6):2859-72
pubmed: 26837576
Cancer Discov. 2017 Jun;7(6):586-595
pubmed: 28365644
Cell. 2022 Feb 3;185(3):563-575.e11
pubmed: 35120664
Nat Genet. 2013 Oct;45(10):1113-20
pubmed: 24071849
J Oncol. 2012;2012:957437
pubmed: 22619677
Nat Genet. 2019 Dec;51(12):1732-1740
pubmed: 31740835
Cancer. 2012 Mar 1;118(5):1422-8
pubmed: 21823111
Nature. 2020 Nov;587(7832):126-132
pubmed: 32879494
Cell. 2018 Apr 5;173(2):321-337.e10
pubmed: 29625050
Nucleic Acids Res. 2020 Feb 28;48(4):1764-1778
pubmed: 31965184
Science. 2017 Jul 28;357(6349):409-413
pubmed: 28596308
NPJ Precis Oncol. 2020 Sep 8;4:27
pubmed: 32964129
Nucleic Acids Res. 2018 Jan 4;46(D1):D1062-D1067
pubmed: 29165669