Predictive Biomarkers to Anti-EGFR Inhibitors Treatment in the Management of Metastatic Colorectal Cancer

Despite the epidermal growth factor receptor (EGFR) monoclonal antibodies (moAbs), cetuximab and panitumumab, have expanded the range of treatment options for metastatic colorectal cancer (mCRC), the prognosis of these patients remains poor. In fact, resistance mechanisms limit the effectiveness of current cancer therapies to treat mCRC. The identification of resistance mechanisms may highlight new biomarkers useful to predict the clinical outcome or the likely responsiveness to pharmacological treatment of those metastatic CRC patients who cannot benefit to anti-EGFR moAbs. Data derived from multiple clinical trials have clearly demonstrated that KRAS mutations can be considered specific negative biomarkers of response to anti-EGFR monoclonal antibodies. Other molecular aberrations in the downstream pathway of EGFR such as BRAF, NRAS, and PIK3CA mutations, and PTEN loss are useful for selecting patients with reduced chance to benefit from anti- EGFR moAbs. The recognition of panels of biomarkers may suggest new strategies to overcome resistance by rational drug design and combination treatment. In this review we discuss the most recent data on predictive and prognostic biomarkers within the EGFR pathway, the challenges this emerging field presents and the future role of these molecular markers in CRC treatment.