Overview
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 treatment dynamics.
The EpiDRIVE study integrates cfDNA 5mC/5hmC sequencing and targeted validation to discover and verify epigenetic determinants of therapeutic response.
Discovery phase: Whole-genome 5mC/5hmC profiling to identify differentially modified regions between responders and non-responders.
Training phase: Targeted sequencing to establish a predictive cfDNA epigenetic panel (EpiDRIVE panel).
Validation phase: qPCR-based validation of selected markers in an independent cohort to confirm predictive accuracy.
This study aims to provide a non-invasive biomarker framework to predict and monitor efficacy of EGFR- and VEGF-targeted therapies in mCRC, ultimately guiding personalized treatment selection.
Eligibility
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.