Since transcriptional reprogramming is the key process in tumor cell adaptation to a heterologous tissue environment (metastasis) and to the survival of therapy, CDK8/19 inhibitors (CDK8/19i) were found to suppress the growth of metastatic tumors preferentially to primary tumors in colon cancer (14) and to prevent tumor adaptation and even overcome the acquired resistance to different classes of anticancer agents, in vitro and in vivo (15–19). The gene discussed is CDK8; the disease is colonic neoplasm.