Biomarker Alteration and frequency Predictive and/or prognostic value References
KRAS Mutations:30-40% Codon 12:70-80% Predictive of resistance to anti-EGFR therapy [13,33-42,47-51]
Codon 13:15-20% Predictive of response to anti-EGFR therapy [47-49]
NRAS Mutations: 3-5% Predictive of worse PFS [45,47,54,55]
BRAF Mutations: 10-15% Both predictive and prognostic [41,43,58,59]
EGFR Copy number Predictive of better prognosis [15-21,24-27]
Overexpression of ligand (amphiregulin and piregulin)
PIK3CA/PTEN Mutations: 10-30% Predictive of lack of response [25,63-73]
HER 3 Overexpression Resistance to cetuximab [75]
HER 2 Amplification: 2% Resistance to cetuximab [76-80]
MET Amplificationand phosphorylation Resistance to cetuximab [81-84]
Table 1: Clinical biomarkers of resistance to EGFR-targeted therapies in CRC.