Many carcinomas, especially those of the gastrointestinal tract have reduced or lost responses to canonical TGFβ signaling through genetic or epigenetic means, including deletion of TGFBR2, TGFBR1, SMAD2, or SMAD4. In such cases, tumor cells no longer show growth inhibition by TGFβ but secrete cytokines that promote tumor progression, for example, by recruiting and polarizing TAMs, immature myeloid cells, or MDSCs (Kitamura et al. 2007, Yang et al. 2008, Yang & Karin 2014). This evidence concerns the gene SMAD4 and neoplasm.