Despite the introduction of multi-agent chemotherapy regimens such as FOLFOX (5-FU, leucovorin, oxaliplatin) and FOLFIRI (5-FU, leucovorin, irinotecan), treatment outcomes in metastatic colorectal cancer (mCRC) remain highly variable.
Current predictive biomarkers, such as RAS/BRAF mutation or microsatellite instability, fail to accurately forecast response to cytotoxic chemotherapy.
Emerging evidence suggests that cfDNA methylation (5mC) and hydroxymethylation (5hmC) patterns reflect tumor biology and drug sensitivity, offering a promising avenue for precision chemotherapy.
The EpiCORE study integrates genome-wide 5mC/5hmC sequencing and targeted validation assays to identify and confirm epigenetic determinants of chemotherapy efficacy.
Discovery phase: Genome-wide 5mC/5hmC profiling of cfDNA from patients treated with first-line FOLFOX or FOLFIRI to identify candidate regions associated with treatment response.
Training phase: Targeted sequencing and model construction based on candidate loci.
Validation phase: qPCR-based testing to confirm predictive accuracy of the finalized EpiCORE panel.
This study aims to establish a robust cfDNA biomarker framework for predicting and monitoring chemotherapy response in mCRC, contributing to individualized therapeutic decision-making.
