IMPDH and GTP Metabolism in Cancer: Mechanisms, Regulation, and Translational Scope.

IF 4.3 2区医学 Q1 Medicine

Cancer Science Pub Date : 2025-10-03 DOI:10.1111/cas.70200

Aki Ogawa-Iio, Koh Takeuchi, Keita Shigemi, Michelle Jane Genoveso, Hiroaki Niitsu, Iemasa Koh, Yusei Ota, Keita Yamane, Takao Hinoi, Natsuki Osaka, Masashi Oshima, Tomohiro Ishikawa, Tomoyuki Mizuno, Manabu Natsumeda, Kensuke Tateishi, Rintaro Hashizume, Satoru Osuka, Susumu Goyama, Tomoharu Yasuda, Toshiya Senda, Atsuo T Sasaki

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引用次数: 0

Abstract

Guanosine triphosphate (GTP) is increasingly recognized as a critical actor in cancer cell proliferation, yet its regulatory mechanism remains incompletely defined. A key contributor to elevated GTP levels in tumors is inosine monophosphate dehydrogenase 2 (IMPDH2), a rate-limiting enzyme in the de novo guanine nucleotide biosynthetic pathway. Although IMPDH inhibitors, mycophenolic acid (MPA) and mycophenolate mofetil (MMF), have shown potential in cancer therapies, their success has been limited due to their immunosuppressive side effects and several unresolved regulatory mechanisms, including paradoxical control of IMPDH activity by GTP. This review provides a systematic summary of the current understanding of IMPDH biology, emphasizing its complex regulation and therapeutic relevance in cancer. We will outline key unresolved questions, including isozyme-specific roles and mechanisms for escaping regulation, and propose mechanistic and translational strategies to design IMPDH-targeted cancer therapies.

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肿瘤中的IMPDH和GTP代谢：机制、调控和翻译范围。

三磷酸鸟苷（Guanosine triphosphate， GTP）被越来越多地认为是癌细胞增殖的关键因素，但其调控机制尚未完全确定。肿瘤中GTP水平升高的关键因素是肌苷单磷酸脱氢酶2 (IMPDH2)，这是一种新的鸟嘌呤核苷酸生物合成途径中的限速酶。虽然IMPDH抑制剂，霉酚酸（MPA）和霉酚酸酯（MMF）在癌症治疗中显示出潜力，但由于其免疫抑制副作用和一些尚未解决的调节机制，包括GTP对IMPDH活性的矛盾控制，它们的成功受到限制。本综述系统总结了目前对IMPDH生物学的认识，强调了其在癌症中的复杂调控和治疗意义。我们将概述关键的未解决的问题，包括同工酶特异性的作用和逃避调节的机制，并提出机制和翻译策略来设计impdh靶向的癌症治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Science ONCOLOGY-

CiteScore

9.90

自引率

3.50%

发文量

406

审稿时长

17 weeks

期刊介绍： Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.