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: 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: 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: 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.
Recommended CitationRao, 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; and Goel, Sanjay, "Excision repair cross-complementing group-1 (ERCC1) induction kinetics and polymorphism are markers of inferior outcome in patients with colorectal cancer treated with oxaliplatin." (2019). Department of Medical Oncology Faculty Papers. Paper 100.
Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.