Anti-Epidermal Growth Factor Receptor (EGFR) Treatment in Patients with Metastatic Colorectal Cancer

Colorectal cancer is one of the most common cancer types and still a major public health problem. Approximately a half of the patients develop metastasis during the course of disease. Prognosis of metastatic colourectal cancer (mCRC) is poor with best supportive care alone (median survival: 6 months). Fortunately, combination chemotherapy has significantly improved survival up to 17-22 months. Cetuximab and panitumumab, the two monoclonal antibodies (mAbs) against epidermal growth factor receptor (EGFR), provide significant clinical benefit in only RAS wild (WT) mCRC. Major side effects are skin toxicity, infusion reactions, fatigue, and electrolyte imbalances. When these mAbs are combined with chemotherapy, overall survival could be as long as 24 months. However, RAS WT status does not ensure response to anti-EGFR mAbs. In addition, RAS WT patients consequently develop resistance to these agents after an initial responsive period. Therefore, understanding the primary and secondary resistance mechanisms apart from RAS status is very important to improve outcomes of mCRC patients. Oncogenic activation of EGFR downstream signaling effectors (KRAS, BRAF, PTEN, and PIK3CA) appears to be the main components of resistance. In future, a comprehensive biomarker analysis will probably help to identify the mCRC patients who will truly benefit from anti-EGFR mAbs.