Adenosine receptors as potential targets in melanoma

Melanoma is one of the most aggressive types of cancer, that is difficult to manage clinically. A major feature of melanoma cells is their ability to escape immune surveillance. Adenosine receptors play a pivotal role in host immune-surveillance. A2a (A2aR) and, partially, A2bR receptors mediate the adenosine-induced immune-suppression, which markedly facilitates tumor development/progression. On the contrary, A3R stimulation enhances the anti-tumor immune response and thus limits tumor growth. A3R also inhibits the proliferation of many cancer cells. Given that A2aR and A3R have profound effects on tumor growth and metastasis, they are attractive targets for novel therapeutic anti-cancer agents. Here, we review the role played by A2aR and A3R in regulating cancer pathogenesis, with a focus on melanoma, and the therapeutic potential of adenosine receptors pharmacological modulation.