EGFR inhibitors have

exhibited single agent activity, and seem to synergize very well with standard chemotherapy except for cetuximab and 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX). Preliminary data suggests that EGFR inhibitors have similar effectiveness to vascular endothelial growth factor (VEGF) inhibitors in the first line setting. Skin toxicity remains the main limiting factor for the utilization of EGFR inhibitors, but strategies including the use of agents such as minocycline or doxycycline added to topical care seem to limit the severity of the rash. Key Words: Epidermal growth factor inhibitors (EGFR inhibitor), metastatic colorectal cancer (mCRC), cetuximab, panitumumab, Inhibitors,research,lifescience,medical KRAS, targeted therapy Introduction Colorectal cancer (CRC) is the 2nd leading cause Inhibitors,research,lifescience,medical of cancer-related death in the Western population and results in approximately 50,000 deaths annually in the United States (1). The incidence and mortality has decreased from 1999-2006, which is attributed

Inhibitors,research,lifescience,medical to improvements in surgical and adjuvant therapy as well as increasing use of screening methods leading to earlier detection. About 20% of patients present with metastatic colorectal cancer (mCRC) and untreated, this group has a median screening libraries overall survival (OS) of 7 months (2) and with therapy, a 5-year survival rate Inhibitors,research,lifescience,medical of 10% (3). The most common sites of metastasis are liver, lymph nodes, lung, and peritoneum. Recent advances in the understanding of tumor biology and genetics has paved the way for targeted therapies and led to improvements in the efficacy of cytotoxic regimens. 5-fluorouracil (FU) has been available for use in CRC for over 60 years and eight additional agents have been approved since Inhibitors,research,lifescience,medical 1996, five of which are targeted therapies. Epidermal growth factor receptor-the target The epidermal growth factor receptor (EGFR) is a 170 kDa receptor tyrosine kinase, and a member of the human epidermal growth factor receptor (HER) or ErbB family. EGFR is also known as the type 1 receptor tyrosine

kinase or ErbB1/HER1. The other members of the family include ErbB2 (HER2/neu), ErbB3 (HER3) and ErbB4 (HER4) (4). EGF is a potent epithelial mitogen in the gastrointestinal tract and can stimulate epithelial proliferation in the neonatal intestine. Furthermore, it can enhance the growth Entinostat of Imatinib Mesylate chemical structure primary colon epithelial cell cultures (4). Most epithelial cancers express EGFR and this growth factor receptor was the first to be proposed as a target for cancer therapy (5). The first anti-EGFR drugs were developed in 1980s and it took over 20 years for the first one to become commercially available. The EGF receptor is composed of an extracellular ligand-binding domain, a transmembrane segment and an intracellular tyrosine kinase domain.