As the cell-autonomous role of adenosine signaling through Adora2b has not been comprehensively studied in pancreatic cancer cells, we will also discuss published data from other malignancies to infer emerging therapeutic considerations for targeting the Adora2b adenosine receptor to reduce the proliferative, invasive, and metastatic potential of PDAC cells. Here, ADORA2B is linked to familial pancreatic carcinoma.