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Adenosine Receptors and Current Opportunities to Treat Cancer

  • Stefania Gessi
  • Stefania Merighi
  • Pier Andrea Borea
  • Shira Cohen
  • Pnina Fishman
Chapter
Part of the The Receptors book series (REC, volume 34)

Abstract

Adenosine is an endogenous modulator exerting its physiological effects by activating four A1, A2A, A2B, and A3 adenosine receptors. This nucleoside increases in hypoxia that characterizes solid tumors, thus affecting vasculature, immunoescaping, and cancer growth. This chapter offers an updated overview on the current opportunities to treat tumors coming from the adenosinergic field. Several years of research has led to the conclusion that A2A and A3 subtypes are the most promising for drug development. As for A3 receptors, consequent to the efficacy of their agonists in numerous animal models of cancer, the lead compound, Namodenoson, has entered in clinical trials for hepatocellular carcinoma. Phase I results proved its optimal safety profile and efficacy, so that phase II studies are in progress. Specifically, A2A receptor is responsible for immunosuppressive effects, reducing antitumor immunity and promoting immunoescaping of cancer. Therefore, A2A receptor antagonists have been proposed to fight cancer by enhancing immunotherapy, supported also by their safety already demonstrated in clinical trials for Parkinson’s disease. Overall, from these positive results, it may be expected that A3 agonists and A2A antagonists may become future anticancer drugs with the ability to save and improve human health also for diseases with very limited treatment options.

Keywords

A2A receptors A3 receptor Cell proliferation Immunoescaping Immunoprotection Clinical trials 

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Stefania Gessi
    • 1
  • Stefania Merighi
    • 1
  • Pier Andrea Borea
    • 1
  • Shira Cohen
    • 2
  • Pnina Fishman
    • 2
  1. 1.Department of Medical SciencesUniversity of FerraraFerraraItaly
  2. 2.Can Fite BiopharmaPetah-TikvaIsrael

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