Interestingly, by seeding a human CRC cell line (HCA-7) in a three-dimensional (3D) culture system in type-I collagen as single cell suspension, Li et al. generated de novo and acquired cetuximab resistant CRC cell lines, SC and CC-CR, respectively, that are WT for KRAS, BRAF, PIK3CA, and EGFR, and not amplified MET, but with increased MET/RON tyrosine phosphorylation (Li et al., 2017; Graves-Deal et al., 2019). Here, PIK3CA is linked to colorectal carcinoma.