A(2B) Adenosine Receptor and Cancer

There are four subtypes of adenosine receptors (ARs), named A(1), A(2A), A(2B) and A(3), all of which are G protein-coupled receptors (GPCRs). Locally produced adenosine is a suppressant in anti-tumor immune surveillance. The A(2B)AR, coupled to both Gαs and Gαi G proteins, is one of the several GPCRs that are expressed in a significantly higher level in certain cancer tissues, in comparison to adjacent normal tissues. There is growing evidence that the A(2B)AR plays an important role in tumor cell proliferation, angiogenesis, metastasis, and immune suppression. Thus, A(2B)AR antagonists are novel, potentially attractive anticancer agents. Several antagonists targeting A(2B)AR are currently in clinical trials for various types of cancers. In this review, we first describe the signaling, agonists, and antagonists of the A(2B)AR. We further discuss the role of the A(2B)AR in the progression of various cancers, and the rationale of using A(2B)AR antagonists in cancer therapy.