Metabolic inhibitors have been used in oncology for decades, dating back to antimetabolites developed in the 1940s. In the past 25 years, there has been increased recognition of metabolic derangements in tumor cells leading to a resurgence of interest in targeting metabolism. More recently there has been recognition that drugs targeting tumor metabolism also affect the often acidic, hypoxic, immunosuppressive tumor microenvironment (TME) and non-tumor cell populations within it, including immune cells. Here we review small-molecule metabolic inhibitors currently in clinical development for oncology applications. For each agent, we evaluate the preclinical studies demonstrating antitumor and TME effects and review ongoing clinical trials. The goal of this Review is to provide an overview of the landscape of metabolic inhibitors in clinical development for oncology.

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肿瘤代谢抑制剂的临床开发

代谢抑制剂在肿瘤学中的应用已有数十年历史，可以追溯到 20 世纪 40 年代开发的抗代谢药物。在过去的 25 年里，人们对肿瘤细胞代谢紊乱的认识不断提高，导致人们对靶向代谢的兴趣重新燃起。最近人们认识到，针对肿瘤代谢的药物也会影响通常呈酸性、缺氧、免疫抑制的肿瘤微环境（TME）和其中的非肿瘤细胞群，包括免疫细胞。在这里，我们回顾了目前用于肿瘤学应用的临床开发中的小分子代谢抑制剂。对于每种药物，我们都会评估证明其抗肿瘤和 TME 效果的临床前研究，并审查正在进行的临床试验。本综述的目的是概述代谢抑制剂在肿瘤学临床开发中的概况。