Meanwhile, the ADRB2-Akt pathway in PDAC activated by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) mediates smoking-induced tumor stemness and gemcitabine resistance by increasing octamer-binding transcription factor-4 (OCT-4), SRY-Box transcription factor 2 (SOX-2), and Nanog in pancreatic cancer cells [108] (Fig.3B). This evidence concerns the gene SOX2 and familial pancreatic carcinoma.