ABSTRACT
This chapter focuses on the epidermal growth factor receptor (EGFR) pathway, the concomitant derangements found in colorectal cancers, and how some of these alterations affect sensitivity and resistance to these targeted treatments. To further improve the treatment of patients with metastatic colorectal cancer (mCRC) it is imperative to identify predictive markers of response or resistance to cetuximab and panitumumab. The first difficulty encountered is that some of these genetic alterations are rare and/or the magnitude of the effect on predicting resistance or sensitivity is small to moderate. Colorectal cancer (CRC) is the third most frequently diagnosed cancer, and the fourth leading cause of cancer deaths worldwide. The benefit of cetuximab and panitumumab in the treatment of patients with mCRC has been clearly demonstrated, albeit with only modest objective response rates of approximately 10% and improvements of survival of 3–4 months. The toxicity profile of the anti-EGFR moAbs excludes several of the severe side effects commonly associated with cytotoxic chemotherapy, such as hematological suppression.
