SMAD4 and cancer: Taken together, the findings in the current study suggest that targeting TGF-β together with JAK1 pathways could be an advantageous approach to suppress cancer cell growth and angiogenesis in PDAC, and raise the possibility that this combination may be especially effective in patients whose tumors have wild-type SMAD4, exhibit HDAC9-positivity, or express an angiogenic gene signature.