Based on our results, trametinib treatment, which inhibits both MEK1 and MEK2, might be an effective therapy in BRAF V600E‐positive/SPINK1‐low subpopulation of patients with CRC, as it led to increased SPINK1 secretion in BRAF V600E‐positive CRC cells. The gene discussed is MAP2K2; the disease is colorectal carcinoma.