However, multiple factors, such as APC, KRAS, TP53, BRAF, PIK3CA [7–9], and especially ErbBs activation leading to the heterogeneity of CRC cells, will cause Intrinsic/acquired resistance and limit the therapeutic efficacy of EGFR-TKI in CRC [10]. The gene discussed is EGFR; the disease is colorectal carcinoma.