Clonal dynamics of circulating tumor DNA during immune checkpoint blockade therapy for melanoma.
Adult
Aged
Aged, 80 and over
Alleles
Circulating Tumor DNA
/ blood
DNA Mutational Analysis
Disease Progression
Female
Humans
Immune Checkpoint Inhibitors
/ therapeutic use
Liquid Biopsy
Longitudinal Studies
Male
Melanoma
/ blood
Middle Aged
Mutation
Retrospective Studies
Skin Neoplasms
/ blood
Treatment Outcome
Tumor Burden
Exome Sequencing
circulating tumor DNA
clonal evolution
immune checkpoint inhibitor
liquid biopsy
melanoma
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Nov 2021
Nov 2021
Historique:
revised:
10
07
2021
received:
23
05
2021
accepted:
15
07
2021
pubmed:
4
9
2021
medline:
24
11
2021
entrez:
3
9
2021
Statut:
ppublish
Résumé
Assessment of treatment efficacy of immune checkpoint inhibitors in melanoma patients is difficult as the response to these therapies varies among patients or lesions. The clonal evolution of cancer during immune checkpoint blockade therapy could cause treatment resistance. We investigated the potential of liquid biopsy in monitoring the mutational profiles of metastatic melanoma during immunotherapy. Plasma samples collected from 21 Japanese metastatic melanoma patients before immune checkpoint blockade therapy were subjected to whole-exome sequencing (WES). Furthermore, 14 Japanese patients with melanoma were enrolled for longitudinal analysis of circulating tumor DNA (ctDNA). Plasma samples were collected prospectively before and during therapy and sequenced. WES of the pretreatment plasma from Japanese melanoma patients showed detectable ctDNA levels with wide ranges of variant allele frequencies within a sample, suggesting clonal and subclonal mutations in ctDNA. In targeted sequencing using longitudinal samples, ctDNA levels correlated with increased tumor size, while ctDNA content immediately decreased after a surge in a patient exhibiting pseudo-progression, suggesting the potential of ctDNA analysis in discriminating between pseudo- and true progression. Mutant ctDNA levels showed different patterns within the clinical course of specific patients, suggesting that these mutations were derived from different tumor clones with distinct therapeutic responses. During further investigation, WES of plasma samples from 1 patient showed marked differences in the mutational profiles of ctDNA, including expansive tumor evolution during an acute exacerbation. Immunotherapy may induce characteristic clonal evolutions of tumors; longitudinal analysis of ctDNA has the potential of determining these tumor evolution patterns and therapeutic responses.
Identifiants
pubmed: 34477284
doi: 10.1111/cas.15088
pmc: PMC8586661
doi:
Substances chimiques
Circulating Tumor DNA
0
Immune Checkpoint Inhibitors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4748-4757Subventions
Organisme : Joint Research Project of the Institute of Medical Science, University of Tokyo
Organisme : Takeda Science Foundation
Organisme : National Cancer Center Research and Development Fund
ID : 25-A-4
Organisme : National Cancer Center Research and Development Fund
ID : 28-A-4
Organisme : National Cancer Center Research and Development Fund
ID : 29-A-6
Organisme : Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University
Organisme : Yakult Bio-Science Foundation
Organisme : Yasuda Memorial Medical Foundation
Organisme : Japan Agency for Medical Research and Development
ID : JP20ck0106558
Organisme : Princess Takamatsu Cancer Research Fund
Organisme : Kobayashi Foundation for Cancer Research
Informations de copyright
© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
Références
Clin Cancer Res. 2019 Jun 15;25(12):3548-3560
pubmed: 30782616
N Engl J Med. 2016 Nov 10;375(19):1823-1833
pubmed: 27718847
Sci Transl Med. 2015 Apr 15;7(283):283ra53
pubmed: 25877891
Clin Cancer Res. 2016 Nov 15;22(22):5480-5486
pubmed: 27482033
N Engl J Med. 2015 Oct 22;373(17):1627-39
pubmed: 26412456
Cancer Discov. 2017 Mar;7(3):264-276
pubmed: 28031159
J Clin Med. 2018 Dec 12;7(12):
pubmed: 30545122
N Engl J Med. 2016 Sep 1;375(9):819-29
pubmed: 27433843
Cell. 2017 Nov 2;171(4):934-949.e16
pubmed: 29033130
J Am Acad Dermatol. 2015 Jun;72(6):1036-46.e2
pubmed: 25819940
Cancer Res. 2007 Oct 1;67(19):9364-70
pubmed: 17909045
N Engl J Med. 2015 Nov 5;373(19):1803-13
pubmed: 26406148
Science. 2015 Apr 3;348(6230):124-8
pubmed: 25765070
J Adv Pract Oncol. 2017 Jan-Feb;8(1):58-72
pubmed: 29900017
N Engl J Med. 2010 Aug 19;363(8):711-23
pubmed: 20525992
Cancer Sci. 2021 Nov;112(11):4748-4757
pubmed: 34477284
Bioinformatics. 2010 Mar 1;26(5):589-95
pubmed: 20080505
J Dermatol Sci. 2017 Jan;85(1):51-57
pubmed: 27771229
N Engl J Med. 2012 Jun 28;366(26):2443-54
pubmed: 22658127
N Engl J Med. 2015 Jan 22;372(4):320-30
pubmed: 25399552
Sci Rep. 2015 Jun 22;5:11198
pubmed: 26095797
Ann Oncol. 2017 May 1;28(5):1130-1136
pubmed: 28327969
Br J Cancer. 2005 Jun 6;92(11):2032-8
pubmed: 15928660
Clin Cancer Res. 2009 Dec 1;15(23):7412-20
pubmed: 19934295
Sci Rep. 2015 Dec 16;5:18425
pubmed: 26669280
Cancer Discov. 2014 Jan;4(1):80-93
pubmed: 24265155
Int J Cancer. 2004 Sep 20;111(5):705-10
pubmed: 15252839
Cancer Res. 2014 May 1;74(9):2465-75
pubmed: 24788099
Cell. 2012 Jul 20;150(2):251-63
pubmed: 22817889
NPJ Genom Med. 2017 Sep 4;2:25
pubmed: 29075515
Br J Dermatol. 2020 Feb;182(2):382-389
pubmed: 31102256
Ann Oncol. 2016 Oct;27(10):1959-65
pubmed: 27502704
Trends Genet. 2018 Aug;34(8):639-651
pubmed: 29903534
N Engl J Med. 2015 Jul 9;373(2):123-35
pubmed: 26028407
Cancer Treat Res. 2016;167:295-320
pubmed: 26601869
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
J Immunother Cancer. 2014 Dec 16;2(1):42
pubmed: 25516806
Exp Dermatol. 2016 Jul;25(7):497-500
pubmed: 27060971
J Dermatol Sci. 2015 Oct;80(1):33-7
pubmed: 26282084