Strategies to overcome resistance to epidermal growth factor receptor monoclonal antibody therapy in metastatic colorectal cancer

Table 1 Components of the epidermal growth factor receptor signaling pathway and their abnormalities in colorectal cancer

Component(gene/protein)	Defect in CRC	Frequency in CRC
EGFR/EGFR	Protein expression	25%-90%
	Mutation	Rare
	Increased copy number	0%-50%
K-ras/K-Ras	Activating mutation	30%-40%
	(exon 2, codon 12, 13, exon 3/4, codon 61, 117, 146)
N-ras/N-Ras	Activating mutation	3%-5%
	(exon 1, codon 12, 13, exon 2, codon 61)
B-Raf/BRAF	Activating mutation (V600E)	10%-15%
PIK3CA/PI3KCA	Activating mutation (exons 9 and 20)	15%-18%
PTEN/PTEN	Loss of protein expression	13%-19%
	Mutation
	Loss of heterozygosity

CRC: Colorectal cancer; EGFR: Epidermal growth factor receptor.