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前列腺癌异质性和可塑性的代谢调控

Metabolic regulation of prostate cancer heterogeneity and plasticity.

作者信息

Peitzsch Claudia, Gorodetska Ielizaveta, Klusa Daria, Shi Qihui, Alves Tiago C, Pantel Klaus, Dubrovska Anna

机构信息

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Tumor Diseases (NCT) Partner Site, Dresden, Germany.

OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Germany.

出版信息

Semin Cancer Biol. 2022 Jul;82:94-119. doi: 10.1016/j.semcancer.2020.12.002. Epub 2020 Dec 5.

Abstract

Metabolic reprogramming is one of the main hallmarks of cancer cells. It refers to the metabolic adaptations of tumor cells in response to nutrient deficiency, microenvironmental insults, and anti-cancer therapies. Metabolic transformation during tumor development plays a critical role in the continued tumor growth and progression and is driven by a complex interplay between the tumor mutational landscape, epigenetic modifications, and microenvironmental influences. Understanding the tumor metabolic vulnerabilities might open novel diagnostic and therapeutic approaches with the potential to improve the efficacy of current tumor treatments. Prostate cancer is a highly heterogeneous disease harboring different mutations and tumor cell phenotypes. While the increase of intra-tumor genetic and epigenetic heterogeneity is associated with tumor progression, less is known about metabolic regulation of prostate cancer cell heterogeneity and plasticity. This review summarizes the central metabolic adaptations in prostate tumors, state-of-the-art technologies for metabolic analysis, and the perspectives for metabolic targeting and diagnostic implications.

摘要

代谢重编程是癌细胞的主要特征之一。它指的是肿瘤细胞为应对营养缺乏、微环境损伤和抗癌治疗而发生的代谢适应。肿瘤发生过程中的代谢转变在肿瘤的持续生长和进展中起着关键作用,并且由肿瘤突变图谱、表观遗传修饰和微环境影响之间的复杂相互作用驱动。了解肿瘤代谢弱点可能会开辟新的诊断和治疗方法,有望提高当前肿瘤治疗的疗效。前列腺癌是一种高度异质性疾病,存在不同的突变和肿瘤细胞表型。虽然肿瘤内遗传和表观遗传异质性的增加与肿瘤进展相关,但关于前列腺癌细胞异质性和可塑性的代谢调节却知之甚少。本综述总结了前列腺肿瘤中的核心代谢适应、代谢分析的最新技术,以及代谢靶向和诊断意义的前景。

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