The transcription factor STAT5b is an antitumor target. STAT5b confers gemcitabine chemoresistance and promotes cell adherence and invasiveness in pancreatic cancer cells. Targeting STAT5b may lead to novel therapeutic strategies for PDAC. Signal transducer and activator of transcription 5b (STAT5b) is a growth hormone (GH)-activated transcription factor and a master regulator of sexually dimorphic gene expression in the liver. Disruption of the GH hypothalamo-pituitary-liver axis controlling STAT5b activation can lead to metabolic dysregulation, steatosis, and liver cancer.