The current focus is on integrating genetic/epigenetic/immune mechanisms in colorectal cancer etiology. The genetic basis of oncology is studied using cultured human cancer cells and preclinical approaches, including the Apc-mutant polyposis in rat colon (Pirc) model coupled to a novel murine polypectomy methodology. Epigenomic aspects are studied through alterations in epigenetic 'readers', 'writers' and 'erasers', via combined deacetylase plus bromodomain inhibition, which also modulates immune-related players in cancer cells. Deacetylase/bromodomain expression and protein acetylation changes also are examined in clinical specimens, organoids, 3D spheroids, and human volunteers undergoing colonoscopy, thereby providing clinical translation of the research.