Anti-Egfr Resistance in Colorectal Cancer: Current Knowledge and Future Perspectives

Anti-EGFR therapy in metastatic colorectal cancer (mCRC) has improved survival outcome. However, many patients do not respond to this therapy and almost all patients develop resistance after a few months of treatment. Since 2008, the therapy has been restricted to patients without mutations in KRAS, an important target in the EGFR pathway, as these patients do not benefit from anti-EGFR therapy. Recently, this has been changed to an all-RAS wild-type strategy. Despite these restrictions, still 40 to 60 % of mCRC patients are resistant. New biomarkers need to be identified in order to improve patient selection. Another problem is tumor heterogeneity, which impedes the detection of mutations in resistance genes and can consequently lead to wrong treatment decisions. A possible solution for this problem may be found in liquid biopsies. In this review, known and promising upcoming biomarkers associated with resistance to antiEGFR therapy will be summarized. Moreover, the potential added value of liquid biopsies in patient selection and followup will be discussed.