靶向 MTHFD2 以利用癌症特异性代谢和 DNA 损伤反应。
Targeting MTHFD2 to exploit cancer-specific metabolism and the DNA damage response.
发表日期：2023 Nov 03
作者：
Louise Ramos, Martin Henriksson, Thomas Helleday, Alanna C Green
来源：
CANCER RESEARCH
摘要：
一碳代谢酶亚甲基四氢叶酸脱氢酶/环水解酶 2 (MTHFD2) 是一个有前景的癌症治疗靶点。 MTHFD2 在多种癌症类型中表达上调，促进癌症生长和转移，并与较差的生存率相关。最近的研究开发了同工酶 MTHFD2 和 MTHFD1 的小分子抑制剂，它们通过不同的机制显示出作为抗癌药物的前景。这篇综述讨论了目前对 MTHFD2 在癌症中的功能的理解以及治疗 MTHFD2 过表达癌症的抑制剂的现状。
The one-carbon metabolism enzyme methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) is a promising therapeutic target in cancer. MTHFD2 is upregulated across numerous cancer types, promotes growth and metastasis of cancer, and correlates with poorer survival. Recent studies have developed small molecule inhibitors of the isozymes MTHFD2 and MTHFD1 that show promise as anti-cancer agents through different mechanisms. This review discusses the current understanding of the function of MTHFD2 in cancer and the status of inhibitors for treating MTHFD2-overexpressing cancers.