Towards individualized treatment prediction and real-time follow-up of metastatic colorectal cancer patients using methylation biomarkers.

Colorectal cancer (CRC) represents the third most common cancer type and second leading cause of cancer mortality worldwide. First-line standard treatment in metastatic CRC (mCRC) involves anti-EGFR therapy, which significantly improves progression-free survival (PFS) and overall survival (OS) in RAS/BRAF wild type patients. However, in this group of wild type patients, the response rate is only 30-50%. This indicates that additional resistance mechanisms exist that need to be discovered. Detection of resistance by conventional methods has several limitations. Therefore, there is a need for new, sensitive and specific biomarkers for mCRC management. Preliminary data have shown that methylated DNA biomarkers are promising in CRC detection and follow-up. in this project, I aim to identify differential methylation signatures that can predict primary anti-EGFR response and detect acquired resistance earlier than CT imaging. I will develop two multiplexed assays using droplet digital PCR. One assay will comprise primary resistance biomarkers, with the aim to develop a prediction test on tissue. Another assay will be developed for blood, where the acquired resistance biomarkers will be deployed as follow-up biomarkers allowing real-time monitoring of patients receiving anti-EGFR therapy. The overall aim is to improve the response prediction of these patients and bring us a step closer to personalized medicine.

Keywords:COLORECTAL CANCER, THERAPY RESISTANCE, METHYLATION, BIOMARKERS

Disciplines:Molecular diagnostics, Epigenetics, Gastro-enterology, Cancer diagnosis