Showler Meredith S, Weiser Brian P
Biology Department, Wheaton College, Wheaton, IL, 60187, USA.
Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ, 08084, USA.
J Transl Med. 2020 Oct 7;18(1):377. doi: 10.1186/s12967-020-02555-x.
It is well established that thymidylate synthase inhibitors can cause cellular toxicity through uracil DNA glycosylase (UNG2)-dependent pathways. Additionally, thymidylate synthase inhibitors and HDAC inhibitors are known to act synergistically in a variety of cancer types. A recent article from J. Transl. Med. links these together by demonstrating widespread depletion of UNG2 levels across a variety of cell lines treated with HDAC inhibitors. Recent findings suggest that UNG2 depletion by HDAC inhibitors would likely be an effective method to sensitize cells to thymidylate synthase inhibitors. This is particularly important for cancer types that are typically resistant to thymidylate synthase inhibitors, such as cells that are deficient in p53 activity.
胸腺嘧啶核苷酸合成酶抑制剂可通过尿嘧啶DNA糖基化酶（UNG2）依赖性途径导致细胞毒性，这一点已得到充分证实。此外，已知胸腺嘧啶核苷酸合成酶抑制剂和组蛋白去乙酰化酶（HDAC）抑制剂在多种癌症类型中具有协同作用。《转化医学杂志》最近的一篇文章通过证明在用HDAC抑制剂处理的多种细胞系中UNG2水平普遍降低，将这些联系在一起。最近的研究结果表明，HDAC抑制剂导致UNG2缺失可能是使细胞对胸腺嘧啶核苷酸合成酶抑制剂敏感的有效方法。这对于通常对胸腺嘧啶核苷酸合成酶抑制剂耐药的癌症类型尤为重要，例如p53活性缺乏的细胞。
