癌细胞维持高水平的活性氧 (ROS) 来驱动其生长，但 ROS 可以通过氧化应激和 DNA 损伤引发细胞死亡。为了在ROS水平升高的情况下生存，癌细胞会激活其抗氧化防御。其中一种防御机制是 MTH1，它是一种酶，可以阻止氧化核苷酸掺入 DNA，从而防止 DNA 损伤并导致癌症扩散。 MTH1 水平在许多癌症中通常升高，因此，抑制 MTH1 是抑制肿瘤生长和转移的一种有吸引力的策略。靶向 MTH1 抑制可以诱导癌细胞中的 DNA 损伤，利用癌细胞对氧化应激的脆弱性并选择性地针对它们进行破坏。以 MTH1 为靶点的癌症治疗很有希望，因为正常细胞的 ROS 水平较低，并且对这些途径的依赖性较小，使得该方法对癌症既有效又具有特异性。本综述旨在研究 MTH1 作为治疗靶点的潜力，特别是在癌症治疗中，提供对其结构、功能和在疾病进展中的作用的详细见解。我们还讨论了各种 MTH1 抑制剂，这些抑制剂已被开发用于选择性诱导癌细胞氧化损伤，尽管它们的有效性各不相同。此外，这篇综述对 MTH1 在癌症预防和各种疾病的氧化应激管理中的作用提供了更深入的机制见解。版权所有 © 2024。由 Elsevier B.V. 出版。

Cancer cells maintain high levels of reactive oxygen species (ROS) to drive their growth, but ROS can trigger cell death through oxidative stress and DNA damage. To survive enhanced ROS levels, cancer cells activate their antioxidant defenses. One such defense is MTH1, an enzyme that prevents the incorporation of oxidized nucleotides into DNA, thus preventing DNA damage and allowing cancer to proliferate. MTH1 levels are often elevated in many cancers, and thus, inhibiting MTH1 is an attractive strategy for suppressing tumor growth and metastasis. Targeted MTH1 inhibition can induce DNA damage in cancer cells, exploiting their vulnerability to oxidative stress and selectively targeting them for destruction. Targeting MTH1 is promising for cancer treatment because normal cells have lower ROS levels and are less dependent on these pathways, making the approach both effective and specific to cancer. This review aims to investigate the potential of MTH1 as a therapeutic target, especially in cancer treatment, offering detailed insights into its structure, function, and role in disease progression. We also discussed various MTH1 inhibitors that have been developed to selectively induce oxidative damage in cancer cells, though their effectiveness varies. In addition, this review provide deeper mechanistic insights into the role of MTH1 in cancer prevention and oxidative stress management in various diseases.Copyright © 2024. Published by Elsevier B.V.