Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Department of Oncology and Metabolism, Weston Park Cancer Centre, University of Sheffield, UK.
Mol Oncol. 2022 Nov;16(21):3792-3810. doi: 10.1002/1878-0261.13227. Epub 2022 May 28.
The exploitation of the DNA damage response and DNA repair proficiency of cancer cells is an important anticancer strategy. The replication and repair of DNA are dependent upon the supply of deoxynucleoside triphosphate (dNTP) building blocks, which are produced and maintained by nucleotide metabolic pathways. Enzymes within these pathways can be promising targets to selectively induce toxic DNA lesions in cancer cells. These same pathways also activate antimetabolites, an important group of chemotherapies that disrupt both nucleotide and DNA metabolism to induce DNA damage in cancer cells. Thus, dNTP metabolic enzymes can also be targeted to refine the use of these chemotherapeutics, many of which remain standard of care in common cancers. In this review article, we will discuss both these approaches exemplified by the enzymes MTH1, MTHFD2 and SAMHD1. © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
利用癌细胞的 DNA 损伤反应和 DNA 修复能力是一种重要的抗癌策略。DNA 的复制和修复依赖于脱氧核苷三磷酸（dNTP）构建块的供应，这些构建块由核苷酸代谢途径产生和维持。这些途径中的酶是有希望的靶点，可以选择性地在癌细胞中诱导有毒的 DNA 损伤。这些相同的途径还激活了代谢物类似物，这是一组重要的化疗药物，它们破坏核苷酸和 DNA 代谢以在癌细胞中诱导 DNA 损伤。因此，dNTP 代谢酶也可以作为靶点，以改进这些化疗药物的使用，其中许多药物仍然是常见癌症的标准治疗方法。在这篇综述文章中，我们将讨论这两种方法，以 MTH1、MTHFD2 和 SAMHD1 这三种酶为例。© 2022 作者。分子肿瘤学由 John Wiley & Sons Ltd 代表欧洲生物化学学会联合会出版。
