The HERACLES study represents an exemplary proof of the importance of the use of CRC PDXs that served as a discovery and confirmatory preclinical platform for the detection of HER2 as a novel biomarker for anti-EGFR treatment resistance [55, 57] and the successful transition of these findings into clinical trials which translated into robust improvement in patient outcomes [58, 59, 61, 167]. This evidence concerns the gene ERBB2 and colorectal carcinoma.