DR-379 Identification of the CDX1/2-GUCY2C-cGMP axis as a driver of primary resistance to anti-EGFR therapies in metastatic colorectal cancer

The approval of anti-EGFR treatments for metastatic colorectal cancer significantly improved patient survival. However, drug resistance remains a significant challenge. Limited biomarkers are available to predict patient responses, leaving many without benefits. This project aims to identify genetic and transcriptomic alterations predicting anti-EGFR therapy response using available sequencing data. We aim to validate preliminary findings suggesting intrinsic resistance in CRC tumors is associated with the CDX1/CDX2-GUCY2C axis loss. Secondary findings will also be considered for further validation using our laboratory data. This research aims to enhance patient selection, offering improved therapeutic options for non-responders, potentially increasing the number of beneficiaries.

Saskia Wilting, Erasmus MC, The Netherlands