Insights from Clinical Trials on A Adenosine Receptor Antagonists for Cancer Treatment.

Accumulation of high concentrations of adenosine (ADO) in the tumor microenvironment represents an important immunosuppressive mechanism that promotes cancer progression through A receptor signaling. While initial clinical trials demonstrated modest anticancer effects of monotherapy with A receptor antagonists, combination approaches, particularly with immune checkpoint inhibitors, have shown enhanced potential across multiple cancer types. This review examines the therapeutic potential of ADO/A receptor modulation in bolstering antitumor immune responses, covering the intricate mechanisms of A receptor signaling and ongoing clinical advancements of A receptor antagonists and dual A/A receptor antagonists. Also, we discuss the pivotal role of rational combination strategies in restoring immunocompetence within the tumor microenvironment, thus offering promising prospects for overcoming immune evasion in cancer therapy.