Adenosine pathway and cancer: where do we go from here?

Increasing evidence supports the occurrence of an intriguing link between tumor onset and development with the microenvironment in which cancer cells are embedded. In this context, a critical role of CD73, in calibrating the duration, magnitude and composition of adenosine signaling in cancer development and progression, has been identified. Adenosine levels are increased in cancer tissues as the result of genetic alterations that occur during tumor progression. Indeed, a rearrangement of the adenosine metabolic machinery has been described within the neoplastic milieu with the aim of amplifying adenosine generation, thereby creating an immune tolerant microenvironment suitable for tumor onset and development. At the same time, adenosine, through the engagement of receptors expressed on neoplastic cells, finely tunes the growth and dissemination of tumor mass, thus interfering with cancer proliferation, apoptosis and metastasis. Based on current knowledge, an improved understanding of how and to what extent adenosine participates to the molecular mechanisms underlying cancer development and diffusion will pave the way toward new therapeutic advances. The discovery and development of drugs targeted on this system might lead to substantial improvements in the clinical management of various cancers.