Zhou Yue, Tao Lei, Zhou Xia, Zuo Zeping, Gong Jin, Liu Xiaocong, Zhou Yang, Liu Chunqi, Sang Na, Liu Huan, Zou Jiao, Gou Kun, Yang Xiaowei, Zhao Yinglan
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
The Laboratory of Anesthesiology and Critical Care Medicine, Translational Neuroscience Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Cancer Metab. 2021 May 10;9(1):22. doi: 10.1186/s40170-021-00250-z.
Human dihydroorotate dehydrogenase (DHODH) is a flavin-dependent mitochondrial enzyme catalyzing the fourth step in the de novo pyrimidine synthesis pathway. It is originally a target for the treatment of the non-neoplastic diseases involving in rheumatoid arthritis and multiple sclerosis, and is re-emerging as a validated therapeutic target for cancer therapy. In this review, we mainly unravel the biological function of DHODH in tumor progression, including its crucial role in de novo pyrimidine synthesis and mitochondrial respiratory chain in cancer cells. Moreover, various DHODH inhibitors developing in the past decades are also been displayed, and the specific mechanism between DHODH and its additional effects are illustrated. Collectively, we detailly discuss the association between DHODH and tumors in recent years here, and believe it will provide significant evidences and potential strategies for utilizing DHODH as a potential target in preclinical and clinical cancer therapies.
人类二氢乳清酸脱氢酶（DHODH）是一种依赖黄素的线粒体酶，催化从头嘧啶合成途径的第四步。它最初是治疗类风湿性关节炎和多发性硬化症等非肿瘤性疾病的靶点，现在正重新成为一种经过验证的癌症治疗靶点。在这篇综述中，我们主要阐述DHODH在肿瘤进展中的生物学功能，包括其在癌细胞从头嘧啶合成和线粒体呼吸链中的关键作用。此外，还展示了过去几十年中开发的各种DHODH抑制剂，并阐述了DHODH与其附加效应之间的具体机制。总的来说，我们在这里详细讨论了近年来DHODH与肿瘤之间的关联，并相信这将为在临床前和临床癌症治疗中利用DHODH作为潜在靶点提供重要证据和潜在策略。
