EGFR Signaling in Colorectal Carcinoma

Table 1

Components of the EGFR signaling pathway important in colorectal cancer.

Component (gene/protein)	Protein function	Defect in CRC	Frequency	Impact
				Prognostic	Predictive (to anti-EGFR therapy)
EGFR/EGFR	Transmembrane tyrosine kinase receptor	Protein expression	25–90%	Controversial	No correlation
		Mutation	Rare	Unknown	Unknown
		Increased copy number	0–50%*	Uncertain	Uncertain
KRas/KRas	GDP-/GTP-binding protein; facilitates ligand-dependent signaling	Activating mutation (codons 12, 13, 61, 146); leads to activation of MAPK pathway	30–40%	Controversial	No response (if KRas is mutated)
BRAF/B-Raf	Serine-threonine protein kinase downstream of KRas	Activating mutation (V600E)	5–12%	Poor prognosis in MSS tumors	No response (if BRAF is mutated)
PIK3CA/PI3K	A key signal transducer in the PI3K-AKT pathway	Activating mutation (exons 9 and 20)	14–18%	Poor prognosis in KRas wt tumors	No response (if exon 20 is mutated)
PTEN/PTEN	A protein tyrosine phosphatase enzyme; inactivates PI3K pathway	Loss of protein expression; mutation; LOH	13–19%	Poor prognosis in KRas wt tumors	No response (possibly)

CRC: colorectal cancer; LOH: loss of heterozygosity; wt: wild-type.
*Low % for high (>10 copies) amplification; higher % for low number of copies (3–5 copies).