In summary, we integrated clinical cohort analysis with experimental validation to elucidate: (a) the distinct clinical relevance of SNAI2 at different disease stages; (b) that T2E‐regulated epigenetic silencing may contribute to dynamic changes in SNAI2 levels in PC; (c) that silencing of SNAI2 is required for cell proliferation and luminal differentiation; (d) that SNAI2 interacts with the tumor microenvironment by activating stroma and increasing immunosuppressive immune cell abundance; (e) that restoring SNAI2 expression by HDAC inhibition reverses dasatinib resistance. The gene discussed is HDAC9; the disease is neoplasm.