Development of a cfDNA 5mC/5hmC-based Epigenetic Biomarker Panel to Identify Determinants of Response In VEGF/EGFR-targeted Therapy for Metastatic Colorectal Cancer
City of Hope Medical Center
Summary
The EpiDRIVE study aims to identify cfDNA-based epigenetic determinants of response in metastatic colorectal cancer (mCRC) patients treated with EGFR- or VEGF-targeted therapy. By integrating 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiling, this study seeks to develop a predictive biomarker panel capable of differentiating responders from non-responders to targeted therapy.
Description
Metastatic colorectal cancer (mCRC) remains one of the leading causes of cancer-related death. Although targeted agents such as anti-EGFR (cetuximab, panitumumab) and anti-VEGF (bevacizumab) therapies have improved survival, treatment response varies widely even among molecularly defined subgroups. Traditional biomarkers, including RAS/BRAF mutation and tumor sidedness, fail to accurately predict therapeutic efficacy. Recent studies highlight the potential of cell-free DNA (cfDNA) methylation (5mC) and hydroxymethylation (5hmC) as sensitive, non-invasive indicators of tumor biology and treat…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Histologically confirmed metastatic colorectal adenocarcinoma (mCRC). * Received EGFR-targeted therapy (cetuximab/panitumumab) or VEGF-targeted therapy (bevacizumab). * Availability of pre-treatment plasma sample for cfDNA analysis. * Documented radiologic response evaluation (RECIST 1.1). * RAS/BRAF mutation status known. Exclusion Criteria: * Inadequate cfDNA quality or low cfDNA yield. * Non-adenocarcinoma histology. * Concurrent or prior other active malignancy. * Active inflammatory or autoimmune disease affecting cfDNA methylation profiles.
Interventions
- Diagnostic TestcfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase)
High-throughput genome-wide sequencing of cfDNA methylation (5mC) and hydroxymethylation (5hmC) profiles from pre-treatment plasma samples in the discovery cohort to identify epigenetic determinants of targeted-therapy response (PFS ≥ 12 months vs \< 12 months).
- Diagnostic TestEpiDRIVE Assay (Targeted Sequencing / qPCR Validation)
Targeted sequencing or qPCR-based validation of cfDNA 5mC/5hmC markers identified from the discovery phase to develop and validate a predictive biomarker model discriminating patients with long vs short progression-free survival after EGFR-/VEGF-targeted therapy.
Location
- City of Hope Medical CenterDuarte, California