Recently, we found that CAFs promote gemcitabine resistance in pancreatic cancer via the TGF-β1/SMAD2/3 pathway and ABCC1 transactivation [38] and revealed that epigenetic modification mechanisms drive gemcitabine resistance in PDAC via LLGL1-associated phosphorylation of ER signaling pathway components [39]. Here, SMAD2 is linked to pancreatic neoplasm.