Purinergic signaling is a fundamental mechanism used by all cells to control their internal activities and interact with the environment. A key component of the purinergic system, the enzyme ecto-5′-nucleotidase (CD73) catalyzes the last step in the extracellular metabolism of ATP to form adenosine. Efforts to harness the therapeutic potential of endogenous adenosine in cancer have culminated in the ongoing clinical development of multiple CD73-targeting antibodies and small-molecule inhibitors. However, recent studies are painting an increasingly complex picture of CD73 mRNA and protein regulation and function in cellular homeostasis, physiological adaptation, and disease development. This review discusses the latest conceptual and methodological advances that are helping to unravel the complexity of this important enzyme that was identified nearly 90 years ago.

嘌呤能信号传导是所有细胞用来控制其内部活动并与环境相互作用的基本机制。胞外 5'-核苷酸酶 (CD73) 是嘌呤能系统的关键组成部分，它催化 ATP 细胞外代谢形成腺苷的最后一步。利用内源性腺苷在癌症中的治疗潜力的努力最终导致了多种 CD73 靶向抗体和小分子抑制剂的持续临床开发。然而，最近的研究描绘了 CD73 mRNA 和蛋白质在细胞稳态、生理适应和疾病发展中的调节和功能日益复杂的情况。这篇综述讨论了最新的概念和方法进展，这些进展有助于揭示这种近 90 年前发现的重要酶的复杂性。