Adenosine binding to ARs on the surface of cancer cells has a profound impact on their biology. For example, the triggering of A1R (337, 338), A2AR (54, 339, 340), and A3R (339, 341–343) induces a variety of cellular responses that augment cancer cell survival such as AKT and ERK1/2 stimulation, as well as Bad inactivation (342). Additional responses to AR signaling contributing to bolstered cancer cell survival include upregulation of Bcl2 (343), downregulation of p53 (338) and Bax (343) as well as aversion of caspase-9 (343) and caspase-3 (54, 343, 344) activation. Paradoxically, extracellular adenosine has also been demonstrated to cause cancer cell death either by setting off A1R (345, 346), A2AR (341, 347), A2BR (348, 349), and A3R (339, 350–354) or via induction of AMPK activation upon its cellular uptake and subsequent conversion to AMP (345).