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.

中文翻译：

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DHODH与癌症：有希望的前景有待探索

人二氢乳清酸脱氢酶（DHODH）是一种黄素依赖性线粒体酶，催化从头合成嘧啶合成途径中的第四步。它最初是用于治疗类风湿性关节炎和多发性硬化症的非肿瘤性疾病的靶标，并且正重新成为癌症治疗的有效治疗靶标。在这篇综述中，我们主要揭示DHODH在肿瘤进展中的生物学功能，包括其在从头嘧啶合成和癌细胞线粒体呼吸链中的关键作用。此外，还展示了在过去几十年中发展起来的各种DHODH抑制剂，并阐明了DHODH及其附加作用之间的具体机制。我们在这里共同详细讨论了DHODH与近年来的肿瘤之间的关系，