The heterogeneity of KRAS mutations in colorectal cancer and its biomarker implications: an ever-evolving story

There was a frisson of expectation in 2008 when multiple retrospective studies all similarly concluded that patients whose colorectal (CRC) cancers harbored a KRAS mutation did not demonstrate benefit from monoclonal anti-epidermal growth factor (EGFR) antibodies; finally personalized medicine was entering the field of CRC therapy. Up to that point monoclonal anti-EGFR therapy had become standard-of-care for patients with refractory CRC, although radiographic responses observed with monotherpy were seen in less than 10% (1). EGFR expression by immunochemistry, assumed to be a relevant biomarker, was determined not to be predictive of efficacy (2).