Table 4.

Summary of potential predictive molecular biomarkers for response to the epidermal growth factor receptor (EGFR)–targeted monoclonal antibodies cetuximab and panitumumab in metastatic colorectal cancer^*

Relationship to response	Biomarker	First author (reference)
Predicts lack of response and now incorporated into clinical practice†	KRAS mutation	Amado (27); Bokemeyer (28); Van Cutsem (29); Table 2, this article; (20,130,131)
Very likely to predict lack of response	Mutation or lack of expression of PTEN; mutation of BRAF or PIK3CA	Frattini (58); Perrone (38); Benvenuti (33); Di Nicolantonio (40); Sartore-Bianchi (72); Di Nicolantonio (132)
May predict lack of response‡	Increased HER2 gene copy number	Finocchiaro (100)
May predict increased likelihood of response	Increased EGFR gene copy number§	Table 3, this article
	Increased EGFR phosphorylation‡	Personeni (81)
	Overexpression of alternative EGFR ligands (amphiregulin and/or epiregulin)‡	Khambata-Ford (59)
	pAKt overexpression‡	Razis (133)
Other potential markers	Markers of angiogenesis and cell cycle regulation; transcription factors (VEGF, IL-8, COX-2, cyclin D, NFκB)‡	Vallböhmer (108); Nagashima (109); Zhang (92)

^*Data are based on analysis of tumor tissue from patients participating in clinical trials. COX-2 = cyclooxygenase-2; HER2 = human epidermal growth factor-2; IL-8 = interleukin-8; NFκB = Nuclear factor kappa B; pAkt = phosphorylated Akt; VEGF = vascular endothelial growth factor.

^†Based on data from a study that prospectively defined biomarker analysis and included a large number of patients (13).

^‡Limited preliminary data.

^§Data need to be confirmed in large patient datasets, preferably with prospective study design.