EGFR and metastatic colorectal cancer: In several patients with non-small cell lung cancer, resistance develops through an acquired activating EGFR mutation, T790M [46]; oncogenic shift or accessory pathway activation [47], such as MET amplification, KRAS activation, and PI3K-Akt pathway mutations; PIK3CA mutations have been associated with resistance to EGFR-targeted monoclonal antibodies in patients with metastatic colorectal cancers.