Excision repair cross-complementing group-1 (ERCC1) induction kinetics and polymorphism are markers of inferior outcome in patients with colorectal cancer treated with oxaliplatin.
ERCC1
FOLFOX
colorectal cancer
oxaliplatin
resistance
Journal
Oncotarget
ISSN: 1949-2553
Titre abrégé: Oncotarget
Pays: United States
ID NLM: 101532965
Informations de publication
Date de publication:
17 Sep 2019
17 Sep 2019
Historique:
received:
24
04
2019
accepted:
17
07
2019
entrez:
1
10
2019
pubmed:
1
10
2019
medline:
1
10
2019
Statut:
epublish
Résumé
ERCC1, a component of nucleotide excision repair pathway, is known to repair DNA breaks induced by platinum drugs. We sought to ascertain if ERCC1 expression dynamics and a single nucleotide polymorphism (SNP) rs11615 are biomarkers of sensitivity to oxaliplatin therapy in patients with colorectal cancer (CRC). Western blot and qPCR for ERCC1 expression was performed from PBMCs isolated from patients receiving oxaliplatin-based therapy at specified timepoints. DNA was also isolated from 59 biorepository specimens for SNP analysis. Clinical benefit was determined using progression free survival (PFS) for metastatic CRC. ERCC1 was induced in PBMC in response to oxaliplatin in 13/25 patients with mCRC (52%). Median PFS with ERCC1 induction was 190d compared to 237d in non-induced patients (HR 2.35, CI 1.005-5.479; p=0.0182). ERCC1 was induced in a sub-population of patients undergoing oxaliplatin treatment, which was associated with poorer outcome, suggesting this could serve as a marker of oxaliplatin response. C/C or C/T genotype in
Sections du résumé
BACKGROUND
BACKGROUND
ERCC1, a component of nucleotide excision repair pathway, is known to repair DNA breaks induced by platinum drugs. We sought to ascertain if ERCC1 expression dynamics and a single nucleotide polymorphism (SNP) rs11615 are biomarkers of sensitivity to oxaliplatin therapy in patients with colorectal cancer (CRC).
METHODS
METHODS
Western blot and qPCR for ERCC1 expression was performed from PBMCs isolated from patients receiving oxaliplatin-based therapy at specified timepoints. DNA was also isolated from 59 biorepository specimens for SNP analysis. Clinical benefit was determined using progression free survival (PFS) for metastatic CRC.
RESULTS
RESULTS
ERCC1 was induced in PBMC in response to oxaliplatin in 13/25 patients with mCRC (52%). Median PFS with ERCC1 induction was 190d compared to 237d in non-induced patients (HR 2.35, CI 1.005-5.479; p=0.0182).
CONCLUSIONS
CONCLUSIONS
ERCC1 was induced in a sub-population of patients undergoing oxaliplatin treatment, which was associated with poorer outcome, suggesting this could serve as a marker of oxaliplatin response. C/C or C/T genotype in
Identifiants
pubmed: 31565185
doi: 10.18632/oncotarget.27140
pii: 27140
pmc: PMC6756860
doi:
Types de publication
Journal Article
Langues
eng
Pagination
5510-5522Informations de copyright
Copyright: © 2019 Rao et al.
Déclaration de conflit d'intérêts
CONFLICTS OF INTEREST The authors declare that they have no conflict of interest. DISCLOSURES The authors have no conflicts of interest to disclose.
Références
Eur J Cancer. 2003 Jan;39(1):112-9
pubmed: 12504667
Bioanalysis. 2013 Feb;5(3):369-91
pubmed: 23394702
Clin Cancer Res. 2004 Aug 1;10(15):4939-43
pubmed: 15297394
Biochimie. 1999 Jan-Feb;81(1-2):15-25
pubmed: 10214906
J Clin Oncol. 2000 Aug;18(16):2938-47
pubmed: 10944126
Toxicology. 2003 Nov 15;193(1-2):79-90
pubmed: 14599769
Prog Nucleic Acid Res Mol Biol. 2005;79:183-235
pubmed: 16096029
J Biol Chem. 1995 Sep 29;270(39):22657-60
pubmed: 7559382
J Clin Oncol. 2004 Jan 1;22(1):23-30
pubmed: 14665611
EMBO J. 1993 Sep;12(9):3685-92
pubmed: 8253090
Int J Cancer. 2000 Mar 20;89(2):160-6
pubmed: 10754494
FEBS J. 2006 Apr;273(8):1600-8
pubmed: 16623697
Lung Cancer. 2012 Jan;75(1):102-9
pubmed: 21676483
BMC Womens Health. 2017 Jun 17;17(1):43
pubmed: 28623887
J Clin Oncol. 2008 Apr 1;26(10):1626-34
pubmed: 18316791
J Clin Oncol. 2001 Dec 1;19(23):4298-304
pubmed: 11731512
J Clin Oncol. 2004 Jan 15;22(2):229-37
pubmed: 14657227
Cancer Treat Rev. 1998 Oct;24(5):331-44
pubmed: 9861196
Cancer Chemother Pharmacol. 2001 Nov;48(5):398-406
pubmed: 11761458
Oncologist. 2007 Jan;12(1):38-50
pubmed: 17227899
Clin Cancer Res. 2005 Sep 1;11(17):6212-7
pubmed: 16144923
Mutat Res. 1997 Sep;382(1-2):13-20
pubmed: 9360634
Annu Rev Biochem. 1996;65:43-81
pubmed: 8811174
Cancer Treat Rev. 2007 Oct;33(6):565-77
pubmed: 17707593
N Engl J Med. 2005 Feb 3;352(5):476-87
pubmed: 15689586
J Clin Oncol. 2007 Jun 1;25(16):2198-204
pubmed: 17470851
Cancer Res. 1990 Apr 15;50(8):2256-60
pubmed: 2180564
Int J Oncol. 2000 Mar;16(3):555-60
pubmed: 10675489
Dig Liver Dis. 2012 Jan;44(1):74-9
pubmed: 21893437
Int J Clin Exp Pathol. 2015 Nov 01;8(11):15065-71
pubmed: 26823845
Curr Cancer Drug Targets. 2003 Feb;3(1):21-9
pubmed: 12570658
Clin Cancer Res. 2011 Mar 15;17(6):1632-40
pubmed: 21278243
Cancer Res. 1987 Jun 1;47(11):3000-4
pubmed: 3552211
Hepatogastroenterology. 2012 Jan-Feb;59(113):130-3
pubmed: 21940361
J Clin Oncol. 2009 Jul 1;27(19):3109-16
pubmed: 19451431
Anticancer Res. 2010 Jul;30(7):2531-8
pubmed: 20682979
Carcinogenesis. 1988 Oct;9(10):1909-11
pubmed: 2458857
Cancer Res. 1995 Jun 1;55(11):2334-7
pubmed: 7757984
Exp Mol Pathol. 2017 Feb;102(1):78-85
pubmed: 28088319
Br J Cancer. 1996 Jun;73(12):1569-75
pubmed: 8664132
J Natl Cancer Inst. 2000 Feb 2;92(3):205-16
pubmed: 10655437
Ann Oncol. 2008 Mar;19(3):508-15
pubmed: 17998284
Oncotarget. 2016 Jun 7;7(23):35159-68
pubmed: 27147577
Chem Rev. 2006 Feb;106(2):253-76
pubmed: 16464005
Mol Diagn Ther. 2011 Jun 1;15(3):159-66
pubmed: 21766907
Nucl Med Mol Imaging. 2015 Jun;49(2):108-14
pubmed: 26085855
Clin Cancer Res. 2008 Mar 1;14(5):1291-5
pubmed: 18316546
Int J Mol Med. 2004 Dec;14(6):959-70
pubmed: 15547660
Fam Cancer. 2016 Jul;15(3):405-12
pubmed: 26875156
Tumour Biol. 2014 May;35(5):4697-704
pubmed: 24443257
Semin Oncol. 2000 Oct;27(5 Suppl 10):96-104
pubmed: 11049040
Biochimie. 2003 Nov;85(11):1083-99
pubmed: 14726015