Personalized treatment for advanced colorectal cancer: KRAS and beyond

Targeted therapies have improved the survival of patients with advanced colorectal cancer (CRC). However, further improvements in patient outcomes may be gained by the development of predictive biomarkers in order to select individuals who are most likely to benefit from treatment, thus personalizing treatment. Using the epidermal growth-factor receptor (EGFR) pathway, we discuss the existing and potential predictive biomarkers in clinical development for use with EGFR-targeted agents in metastatic CRC. The data and technological issues surrounding such biomarkers as expression of EGFR or its family members or ligands, KRAS-, NRAS-, and BRAF-mutation status, PI3K/PTEN expression, and imaging and clinical biomarkers, such as rash and hypomagnesemia, are summarized. Although the discovery of KRAS mutations has improved patient selection for EGFR-targeted treatments, further biomarkers are required, especially for those patients who exhibit KRAS mutations rather than the wild-type gene.