The epidermal growth factor receptor (EGFR) is overexpressed in as many as 77% 
of colorectal cancer (CRC) cases. The EGFR is known to be involved in 
carcinogenetic processes such as cell proliferation, apoptosis, angiogenesis, 
cell motility, and metastasis. Preclinical and clinical studies have shown that 
targeting EGFR is a valid strategy for anticancer therapy. Currently, 2 classes 
of anti-EGFR agents are in phase II/III clinical development: monoclonal 
antibodies and tyrosine kinase (TK) inhibitors. The most established monoclonal 
antibody is cetuximab, the only EGFR inhibitor that is currently approved for 
use in patients with metastatic CRC. Several clinical studies of cetuximab, as a 
single agent or in combination with irinotecan, have shown promising efficacy in 
patients with metastatic CRC. Two other monoclonal antibodies, matuzumab (EMD 
72000) and panitumumab (ABG-EGF), also have shown activity against 
EGFR-expressing CRC but are still in the early stage of clinical development. 
The activity of the EGFR TK inhibitors erlotinib and gefitinib have already been 
investigated in clinical phase III trials in patients with non-small-lung 
cancer, suggesting that sequential rather than concurrent 
erlotinib/gefitinib-based treatment provides a benefit in clinical outcome. The 
EGFR-targeting agents are reasonably well tolerated and have limited overlapping 
toxicities in combination with other cytotoxic drugs. The most common side 
effect of anti-EGFR treatment is an acneiform skin rash, which is associated 
with the clinical outcome of treatment with monoclonal antibodies and TK 
inhibitors. Future clinical studies are needed to establish these EGFR-targeting 
agents in anticancer treatment to investigate efficacy of therapies combining 
EGFR-targeted agents with other targeting agents and to describe additional 
markers determining the clinical outcome of anti-EGFR therapy.