For example, we provide evidence that trametinib is deacetylated by Histone Deacetylase 1 (HDAC1); combining trametinib with the HDAC1 inhibitor vorinostat proved potent in both Drosophila and mouse RAS-APC-P53 CRC models, addressing the most frequent three-mutation combination reported for CRC patients. The gene discussed is HDAC1; the disease is colorectal carcinoma.