Predictive and prognostic biomarkers with therapeutic targets in advanced colorectal cancer

Table 1 Predictive and prognostic biomarkers for biological therapy in metastatic colorectal cancer

Biomarker	Prevalence	Evidence available	Predictive and prognostic value
KRAS mutations	40%	Conclusive	Negative predictive biomarker for anti-EGFR mAbs
		Insufficient	Predicts poor prognosis, but not an independent prognostic factor
BRAF mutations	10%	Substantial	Prognostic marker for poor outcome
		Insufficient	Potential predictive marker for resistance to anti-EGFR mAbs
NRAS mutations	3%-5%	Insufficient1	Potential predictive marker for resistance to anti-EGFR mAbs
PIK3CA mutations	15%-20%	Insufficient1	Potential predictive marker for resistance to cetuximab (exon 20, not exon 9 mutations)
			Potential prognostic marker for poor outcome
PTEN (loss of expression)	20%-40%	Insufficient1	Potential predictive marker for resistance to cetuximab
			Associated with activation of the PIK3CA pathway and adverse disease outcome
P53 mutations	1%-5%	Insufficient1	An independent predictive factor for cetuximab benefit
			Not prognostic
Epiregulin, amphiregulin (high expression)	50%-60%	Insufficient1	Associated with resistance to anti-EGFR antibody therapy and adverse clinical outcome
VEGF-D	40%-75%	Insufficient1	Potential predictive marker for response to bevacizumab
VEGF-A		Insufficient1	Not predictive of response to bevacizumab

¹Insufficient: The current clinical evidence cannot definitively demonstrate that the biomarker has predictive or prognostic value in metastatic colorectal cancer. EGFR: Epidermal growth factor receptor; VEGF: Vascular endothelial growth factor.

Table 2 Summary of key biomarkers investigated in clinical trials of bevacizumab

Key biomarkers evaluated
KRAS mutational status
BRAF mutational status
p53 mutational status
VEGF and VEGFR-2 (KDR) gene expression
VEGF A- to VEGF-D, VEGFR-1, and VEGFR-2 protein expression
CD31 expression
Neuropilin expression
Stromal thrombospondin-2 expression
Microvessel density
Plasma VEGF levels

VEGF: Vascular endothelial growth factor.