文章：

磷酸肌肽激酶在癌症中的作用：从分子机制到治疗机会

Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities

原文发布日期：2025-04-03

DOI: 10.1038/s41568-025-00810-1

类型: Review Article

开放获取: 否

英文摘要：

Phosphoinositide kinases, extending beyond the well-known phosphoinositide 3-kinase (PI3K), are key players in the dynamic and site-specific phosphorylation of lipid phosphoinositides. Unlike PI3Ks, phosphatidylinositol 4-kinases (PI4Ks) and phosphatidylinositol phosphate kinases (PIPKs) do not usually exhibit mutational alterations, but mostly show altered expression in tumours, orchestrating a broad spectrum of signalling, metabolic and immune processes, all of which are crucial in the pathogenesis of cancer. Dysregulation of PI4Ks and PIPKs has been associated with various malignancies, which has sparked considerable interest towards their therapeutic targeting. In this Review we summarize the current understanding of the lesser-studied phosphoinositide kinase families, PI4K and PIPK, focusing on their functions and relevance in cancer. In addition, we provide an overview of ongoing efforts driving the preclinical and clinical development of phosphoinositide kinase-targeting molecules.

摘要翻译： 

磷酸肌醇激酶家族不仅包含广为人知的磷酸肌醇3-激酶（PI3K），更是脂质磷酸肌醇动态位点特异性磷酸化的关键调控者。与PI3K不同，磷脂酰肌醇4-激酶（PI4K）和磷脂酰肌醇磷酸激酶（PIPK）通常不表现为基因突变，但在肿瘤中多呈现表达水平异常，通过协调广泛的信号传导、代谢及免疫进程，在癌症发病机制中发挥关键作用。PI4K与PIPK的失调与多种恶性肿瘤相关，这激发了针对其治疗靶点的广泛研究兴趣。本文综述了当前对PI4K和PIPK这两个研究相对较少的磷酸肌醇激酶家族的认识，重点探讨其在癌症中的功能与临床意义，同时概述了推动磷酸肌醇激酶靶向分子从临床前到临床开发的研究进展。

原文链接：

Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities