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Metabolic rearrangements in primary liver cancers: cause and consequences.
Nature Reviews Gastroenterology & Hepatology ( IF 65.1 ) Pub Date : 2019-10-30 , DOI: 10.1038/s41575-019-0217-8
Letizia Satriano 1 , Monika Lewinska 1 , Pedro M Rodrigues 2 , Jesus M Banales 2, 3, 4 , Jesper B Andersen 1
Affiliation  

Primary liver cancer (PLC) is the fourth most frequent cause of cancer-related death. The high mortality rates arise from late diagnosis and the limited accuracy of diagnostic and prognostic biomarkers. The liver is a major regulator, orchestrating the clearance of toxins, balancing glucose, lipid and amino acid uptake, managing whole-body metabolism and maintaining metabolic homeostasis. Tumour onset and progression is frequently accompanied by rearrangements of metabolic pathways, leading to dysregulation of metabolism. The limitation of current therapies targeting PLCs, such as hepatocellular carcinoma and cholangiocarcinoma, points towards the importance of deciphering this metabolic complexity. In this Review, we discuss the role of metabolic liver disruptions and the implications of these processes in PLCs, emphasizing their clinical relevance and value in early diagnosis and prognosis and as putative therapeutic targets. We also describe system biology approaches able to reconstruct the metabolic complexity of liver diseases. We also discuss whether metabolic rearrangements are a cause or consequence of PLCs, emphasizing the opportunity to clinically exploit the rewired metabolism. In line with this idea, we discuss circulating metabolites as promising biomarkers for PLCs.

中文翻译:

原发性肝癌中的代谢重排:原因和后果。

原发性肝癌(PLC)是与癌症相关的死亡的第四大最常见原因。高死亡率源自晚期诊断以及诊断和预后生物标志物的准确性有限。肝脏是主要的调节器,负责协调毒素的清除,平衡葡萄糖,脂质和氨基酸的摄入量,管理全身新陈代谢并维持新陈代谢的体内平衡。肿瘤的发作和发展常常伴随着代谢途径的重排,从而导致代谢失调。目前针对PLC的治疗方法的局限性,例如肝细胞癌和胆管癌,指出了解密这种代谢复杂性的重要性。在这篇评论中,我们讨论了代谢性肝功能衰竭的作用以及这些过程在PLC中的意义,强调其在早期诊断和预后中的临床相关性和价值,并作为推定的治疗靶标。我们还描述了能够重建肝脏疾病代谢复杂性的系统生物学方法。我们还讨论了代谢重排是PLC的原因还是结果,强调了临床上利用重新连接的代谢的机会。根据这一想法,我们讨论循环代谢物作为PLC的有前途的生物标志物。
更新日期:2019-10-30
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