Novel therapeutic agents targeting the epidermal growth factor receptor
(EGFR) have improved outcomes for patients with colorectal carcinoma.
However, these therapies are effective only in a subset of patients.
Activating mutations in the KRAS gene are found in 30-40% of colorectal
tumors and are associated with poor response to anti-EGFR therapies.
Thus, KRAS mutation status can predict which patient may or may not
benefit from anti-EGFR therapy. Although many diagnostic tools have been
developed for KRAS mutation analysis, validated methods and standardized
testing procedures are lacking. This poses a challenge for the optimal
use of anti-EGFR therapies in the management of colorectal carcinoma.
Here we review the molecular basis of EGFR-targeted therapies and the
resistance to treatment conferred by KRAS mutations. We also present
guideline recommendations and a proposal for a European quality
assurance program to help ensure accuracy and proficiency in KRAS
mutation testing across the European Union