In the present study, we evaluated the combined effect of multi-kinase inhibitor regorafenib and pan-PKD inhibitor CRT0066101 against 4 human CRC cells (including HCT116, HCT116 p53−/−, RKO and, HT-29), with each cell line having different mutation profiles in KRAS, BRAF, PI3KCA, and TP53 genes. Here, KRAS is linked to colorectal carcinoma.