Adenosine Receptor Antagonists to Combat Cancer and to Boost Anti-Cancer Chemotherapy and Immunotherapy

Extracellular adenosine accumulates in the environment of numerous tumors. For years, this fact has fueled preclinical research to determine whether adenosine receptors (ARs) could be the target to fight cancer. The four ARs discovered so far, A(1), A(2A), A(2B) and A(3), belong to the class A family of G protein-coupled receptors (GPCRs) and all four have been involved in one way or another in regulating tumor progression. Prompted by the successful anti-cancer immunotherapy, the focus was placed on the ARs more involved in regulation of immune cell differentiation and activation and that are able to establish molecular and functional interactions. This review focuses on the potential of A(2A) and A(2B) receptor antagonists in cancer control and in boosting anti-cancer chemotherapy and immunotherapy. The article also overviews the ongoing clinical trials in which A(2A)R and A(2B)R ligands are being tested in anti-cancer therapy.