科學家總結腫瘤代謝異質性的機制和意義
作者:
小柯機器人發布時間:2019/9/4 15:00:15
美國德克薩斯大學西南醫學中心Ralph J. DeBerardinis等研究人員在2019年9月3日出版的《細胞—代謝》上發表了綜述,在這篇綜述中他們總結了腫瘤代謝異質性的機制和意義。
研究人員表示,腫瘤表現出代謝重塑的活性,從而促進癌症進展。
人們目前對控制體內腫瘤代謝的過程以及鑑定腫瘤代謝弱點的有效手段了解有限。雖然許多文獻都側重於刻板的、細胞自主的途徑,如糖酵解,但最近的工作強調了腫瘤之間甚至在實體腫瘤的不同區域內的代謝的異質性和靈活性。代謝異質性很重要,因為它會影響治療的弱點並可能預測臨床結果。這篇綜述描述了當前關於腫瘤代謝調節的概念,重點關注癌細胞固有的過程以及腫瘤微環境對癌細胞施加的因素。研究人員討論了在臨床前癌症模型中鑑定亞型選擇性代謝弱點的實驗方法。最後,研究人員總結了人們在原發性人類腫瘤中表徵代謝的付出,這應該在臨床相關微環境的背景下產生對代謝異質性的新見解。
附:英文原文
Title: Mechanisms and Implications of Metabolic Heterogeneity in Cancer
Author: Jiyeon Kim, Ralph J. DeBerardinis,et al
Issue&Volume: Volume 30 Issue 3
Abstract: Tumors display reprogrammed metabolic activities that promote cancer progression. We currently possess a limited understanding of the processes governing tumor metabolism in vivo and of the most efficient approaches to identify metabolic vulnerabilities susceptible to therapeutic targeting. While much of the literature focuses on stereotyped, cell-autonomous pathways like glycolysis, recent work emphasizes heterogeneity and flexibility of metabolism between tumors and even within distinct regions of solid tumors. Metabolic heterogeneity is important because it influences therapeutic vulnerabilities and may predict clinical outcomes. This Review describes current concepts about metabolic regulation in tumors, focusing on processes intrinsic to cancer cells and on factors imposed upon cancer cells by the tumor microenvironment. We discuss experimental approaches to identify subtype-selective metabolic vulnerabilities in preclinical cancer models. Finally, we describe efforts to characterize metabolism in primary human tumors, which should produce new insights into metabolic heterogeneity in the context of clinically relevant microenvironments.
DOI: https://doi.org/10.1016/j.cmet.2019.08.013
Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30442-5#