Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Australia.
Trends Pharmacol Sci. 2019 Nov;40(11):866-882. doi: 10.1016/j.tips.2019.09.006. Epub 2019 Oct 31.
Pathogens and tumor cells have adopted various adept strategies to evade immunosurveillance and promote their growth and survival. There has been substantial evidence demonstrating phosphoinositide lipids and their modifying enzymes as essential host targets that are often hijacked by pathogens and tumor cells. The common dependence of pathogen virulence and tumor progression on phosphoinositides presents an exciting disease-combating potential, particularly combinatorial therapeutics. While traditional approaches to pharmacologically inhibit phosphoinositide-metabolizing enzymes has shown some promise, the direct targeting of phosphoinositides has recently emerged as a novel therapeutic strategy. Our review provides a current picture of the role of phosphoinositides during pathogen virulence and tumorigenesis as well as a thorough discussion on promises, challenges, and new perspectives of phosphoinositide-targeting drug development.
病原体和肿瘤细胞已经采用了各种巧妙的策略来逃避免疫监视,并促进其生长和存活。有大量证据表明,磷酸肌醇脂质及其修饰酶是宿主的重要靶点,这些靶点经常被病原体和肿瘤细胞劫持。病原体毒力和肿瘤进展对磷酸肌醇的普遍依赖为疾病的治疗提供了巨大的潜力,尤其是联合治疗。虽然用药理学方法抑制磷酸肌醇代谢酶的传统方法显示出了一些希望,但直接针对磷酸肌醇作为一种新的治疗策略最近出现了。我们的综述提供了磷酸肌醇在病原体毒力和肿瘤发生过程中的作用的最新图片,并对磷酸肌醇靶向药物开发的前景、挑战和新观点进行了全面的讨论。