Department of Neurosurgery, Robert Wood Johnson & New Jersey Medical Schools, Rutgers University, Piscataway, NJ 08854, USA; Rutgers Brain Health Institute, Piscataway, NJ 08854, USA.
MediCity Research Laboratory, University of Turku, Tykistökatu 6A, Turku, 20520, Finland.
Cancer Cell. 2019 Dec 9;36(6):582-596. doi: 10.1016/j.ccell.2019.10.007.
Adenosine is a key metabolic and immune-checkpoint regulator implicated in the tumor escape from the host immune system. Major gaps in knowledge that impede the development of effective adenosine-based therapeutics include: (1) lack of consideration of redundant pathways controlling ATP and adenosine levels; (2) lack of distinction between receptor-dependent and -independent effects of adenosine, and (3) focus on extracellular adenosine without consideration of intracellular metabolism and compartmentalization. In light of current clinical trials, we provide an overview of adenosine metabolism and point out the need for a more careful evaluation of the entire purinome in emerging cancer therapies.
腺苷是一种关键的代谢和免疫检查点调节剂，参与肿瘤逃避宿主免疫系统。阻碍有效的基于腺苷的治疗药物发展的主要知识空白包括：（1）缺乏对控制 ATP 和腺苷水平的冗余途径的考虑；（2）缺乏对腺苷受体依赖性和非依赖性作用的区分；以及（3）关注细胞外腺苷，而不考虑细胞内代谢和区室化。鉴于当前的临床试验，我们对腺苷代谢进行了概述，并指出在新兴的癌症治疗中需要更仔细地评估整个嘌呤组。
