All these findings support the central hypothesis (Fig. 1): Relative levels of Sam68 and Pygo2 affect CBP-Wnt and p300-Wnt activities, influencing response to ICG-001 and resistance to butyrate and other HDACis; thus, modulation of Sam68 and Pygo2 can enhance response to ICG-001 and HDACis, leading to more optimal preventive and therapeutic approaches against CRC. The gene discussed is EP300; the disease is colorectal carcinoma.