To further evaluate the therapeutic implications, we analyzed DepMap CRC cell lines (n = 28) and found that NRG1 promoter methylation was inversely correlated with cetuximab AUC (Spearman R = - 0.527, P = 0.004) (Figure 10E), implying that NRG1 de-methylation/up-regulation may attenuate cetuximab activity via ERBB2–ERBB3 bypass under EGFR blockade. This evidence concerns the gene EGFR and colorectal carcinoma.