In KRAS mutant CRC cells, high expression of SET domain bifurcated histone lysine methyltransferase (SETDB1) resulted in trimethylation of AKT (site not reported), which promoted AKT phosphorylation, resulting in activation of PI3K-AKT pathway. SETDB1-Akt pathway increased glycolysis and increased cell proliferation, all of which contributed to cetuximab resistance. Inhibition of SETDB1 sensitized CRC to cetuximab, independent of KRAS mutation status. This evidence concerns the gene SET and colorectal carcinoma.