In parallel to the influence of the stroma on the local tumor cell behavior, increasing evidence indicates that PDAC cells with epithelial (classical) and mesenchymal (squamous) molecular profiles have the ability to interconvert among the different phenotypic states [63,65] after chemotherapy [136], modulation of key molecular genes (HNF4A, GATA6, and GLI1/2) [56,67,141,142], in response to TGF-β [68,136] and/or under the influence of the TME due to re-shaping of the transcriptional programs of tumor cells [56,143]. The gene discussed is HNF4A; the disease is neoplasm.