Llorente Alicia, Arora Gurpreet K, Murad Rabi, Emerling Brooke M
Cancer Metabolism and Microenvironment Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Bioformatics Core, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Nat Rev Cancer. 2025 Apr 3. doi: 10.1038/s41568-025-00810-1.
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.
磷酸肌醇激酶，其范围超出了广为人知的磷酸肌醇3激酶（PI3K），是脂质磷酸肌醇动态和位点特异性磷酸化的关键参与者。与PI3K不同，磷脂酰肌醇4激酶（PI4K）和磷脂酰肌醇磷酸激酶（PIPK）通常不表现出突变改变，但大多在肿瘤中表现出表达改变，协调广泛的信号传导、代谢和免疫过程，所有这些在癌症发病机制中都至关重要。PI4K和PIPK的失调与各种恶性肿瘤有关，这引发了对其治疗靶点的极大兴趣。在本综述中，我们总结了目前对研究较少的磷酸肌醇激酶家族PI4K和PIPK的理解，重点关注它们在癌症中的功能和相关性。此外，我们概述了推动磷酸肌醇激酶靶向分子临床前和临床开发的正在进行的努力。
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