Development of a cfDNA 5mC/5hmC-based Epigenetic Biomarker Panel to Predict Chemotherapy Efficacy in Metastatic Colorectal Cancer
City of Hope Medical Center
Summary
The EpiCORE study aims to identify cfDNA-based epigenetic markers predictive of response to first-line chemotherapy (FOLFOX or FOLFIRI) in metastatic colorectal cancer (mCRC). By integrating 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiling, this study seeks to establish a non-invasive biomarker panel capable of distinguishing responders from non-responders.
Description
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 stu…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Histologically confirmed metastatic colorectal adenocarcinoma (mCRC). * Received first-line chemotherapy (FOLFOX or FOLFIRI). * Availability of pre-treatment serum or plasma samples for cfDNA 5mC/5hmC analysis. * Documented radiologic or clinical response evaluation (RECIST 1.1 or PFS-based). * RAS/BRAF mutation status available. Exclusion Criteria: * Inadequate cfDNA yield or poor DNA quality. * Non-adenocarcinoma histology. * Active inflammatory or autoimmune disease that may alter cfDNA methylation. * Concomitant malignancy requiring systemic therapy.
Interventions
- Diagnostic TestcfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase)
Genome-wide profiling of cfDNA methylation and hydroxymethylation from pre-treatment plasma to identify molecular determinants associated with chemotherapy efficacy (PFS ≥ 12M vs \< 12M).
- Diagnostic TestEpiCORE Assay (Targeted Sequencing / qPCR Validation)
Targeted validation of cfDNA 5mC/5hmC markers from discovery phase using sequencing and qPCR to build and validate a predictive model for first-line chemotherapy response.
Location
- City of Hope Medical CenterDuarte, California