Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/21868
Title: Excision repair cross-complementing group-1 (ERCC1) induction kinetics and polymorphism are markers of inferior outcome in patients with colorectal cancer treated with oxaliplatin.
Austin Authors: Rao, Devika;Mallick, Atrayee Basu;Augustine, Titto;Daroqui, Cecilia;Jiffry, Jeeshan;Merla, Amartej;Chaudhary, Imran;Seetharam, Raviraja;Sood, Arjun;Gajavelli, Srikanth;Aparo, Santiago;Rajdev, Lakshmi;Kaubisch, Andreas;Chuy, Jennifer;Negassa, Abdissa;Mariadason, John M ;Maitra, Radhashree;Goel, Sanjay
Affiliation: Department of Medical Oncology, Montefiore Medical Center, Bronx, New York, USA
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA
Department of Medical Oncology, Montefiore Medical Center, Bronx, New York, USA
Gastrointestinal Cancers Program and Oncogenic Transcription Laboratory, Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Medical Oncology, Montefiore Medical Center, Bronx, New York, USA
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA
Department of Medical Oncology, Montefiore Medical Center, Bronx, New York, USA
Department of Medicine, Albert Einstein College of Medicine, Bronx, New York, USA
Department of Medical Oncology, Montefiore Medical Center, Bronx, New York, USA
Department of Epidemiology and Biostatistics, Albert Einstein College of Medicine, Bronx, New York, USA
La Trobe University School of Cancer Medicine, Melbourne, Australia
Issue Date: 17-Sep-2019
metadata.dc.date: 2019-09-17
Publication information: Oncotarget 2019; 10(53): 5510-5522
Abstract: 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 rs11615 SNP analysis revealed that 43.3% harbored C/C, 41.2%-T/C and 15.5%-T/T genotype. Median PFS was significantly lower with C/C or T/C (211 and 196d) compared to T/T (590d; p=0.0310). 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 ERCC1 rs11615 locus decreased benefit from oxaliplatin.
URI: http://ahro.austin.org.au/austinjspui/handle/1/21868
DOI: 10.18632/oncotarget.27140
ORCID: 0000-0001-9123-7684
PubMed URL: 31565185
Type: Journal Article
Subjects: ERCC1
FOLFOX
colorectal cancer
oxaliplatin
resistance
Appears in Collections:Journal articles

Show full item record

Page view(s)

2
checked on Nov 29, 2022

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.