A glance at adenosine receptors: novel target for antitumor therapy

Adenosine can be released from a variety of cells throughout the body, as the result of increased metabolic rates, in concentrations that can have a profound impact on the vasculature, immunoescaping, and growth of tumor masses. It is recognized that the concentrations of this nucleoside are increased in cancer tissues. Therefore, it is not surprising that adenosine has been shown to be a crucial factor in determining the cell progression pathway, either during apoptosis or during cytostatic state. From the perspective of cancer, the most important question then may be "Can activation and/or blockade of the pathways downstream of the adenosine receptor contribute to tumor development?" Rigorous examinations of the role of adenosine in in vivo and in vitro systems need to be investigated. The present review therefore proposes multiple adenosine-sustained ways that could prime tumor development together with the critical combinatorial role played by adenosine receptors in taking a choice between proliferation and death. This review proposes that adenosine acts as a potent regulator of normal and tumor cell growth. It is hypothesized that this effect is dependent on extracellular adenosine concentrations, cell surface expression of different adenosine receptor subtypes, and signal transduction mechanisms activated following the binding of specific agonists. We venture to suggest that the clarification of the role of adenosine and its receptors in cancer development may hold great promise for the treatment of chemotherapy in patients affected by malignancies. (C) 2003 Elsevier Inc. All rights reserved.