For some agents, assessment of tumors from patients with responses in phase I or II trials led to the discovery of important, previously-unappreciated biomarkers (e.g., EGFR activating mutations for erlotinib and gefitinib in NSCLC [72,73], EML4/ALK fusions for crizotinib in NSCLC [74], and KRAS mutation status for cetuximab in colorectal cancer [53]). This evidence concerns the gene EML4 and colorectal cancer.