肿瘤是一种代谢性疾病  

Cancer is a metabolic disease

作　　者：石汉平 SHI Han-ping(Department of Gastrointestinal Surgery,Department of Clinical Nutrition,Beijing Shijitan Hospital,Beijing 100038,China;Department of Oncology,Capital Medical University,Beijing 100038,China)

机构地区：[1]首都医科大学附属北京世纪坛医院胃肠外科/临床营养科,北京100038 [2]首都医科大学肿瘤学系,北京100038

出　　处：《肿瘤代谢与营养电子杂志》2018年第2期111-116,共6页Electronic Journal of Metabolism and Nutrition of Cancer

基　　金：国家重点研发计划项目(2017YFC1309200)

摘　　要：肿瘤的生物学本质是什么?是遗传性疾病还是代谢性疾病?这个问题是决定肿瘤治疗方向的重大问题,对这个问题的认识历史上有过反复。研究发现人类有1,000种肿瘤相关基因,其中癌基因大约250种,抑癌基因约700种,其中绝大多数在细胞代谢中发挥关键作用,主要涉及5条代谢途径:(1)有氧糖酵解(aerobic glycolysis)、(2)谷氨酰胺分解(glutaminolysis)、(3)一碳代谢(one-carbon metabolism)、(4)磷酸戊糖通路(pentosephosphate pathway)及(5)脂肪酸从头合成(de novo synthesize fatty acids)。代谢物组学(metabolomics)及肿瘤代谢产物(oncometabolites)研究发现,上述5条代谢通路使肿瘤细胞由单纯的产生ATP转变为产生大量氨基酸、核苷酸、脂肪酸以及细胞快速生长与增殖需要的其他中间产物,这些代谢产物反过来服务于上述代谢通路,从而促进肿瘤生长、抑制肿瘤凋亡。因此,本文认为肿瘤是一种代谢性疾病,我们应该据此调整肿瘤的治疗策略与方向,肿瘤营养与代谢调节治疗应该也必将成为肿瘤治疗的主战场。鉴于肿瘤细胞的高度代谢适应性,遭遇任何应激伤害时会自动切换或启用其他通路,所以肿瘤代谢调节治疗应该联合阻断或调控多个代谢途径。What is the biological nature of cancer?Is cancer a genetic disease or a metabolic disease?Controversy exists in history about this question which is a fundamental issue that determines the cancer treatment strategy.Genetic analysis has revealed that there are nearly 1,000 known cancer-associated genes in humans,including^250 oncogenes and^700 tumor suppressors.Many of these cancer genes play a key role in cell metabolism,mainly affecting five major metabolic pathways:1)aerobic glycolysis,2)glutaminolysis,3)one-carbon metabolism,4)pentosephosphate pathway and 5)de novo synthesize fatty acids.Studies via metabolomics and oncometabolites indicate that the above pathways allow cancer cells to shift from simply producing ATP to generating large quantities of amino acids,nucleotides,fatty acids and other intermediates needed for rapid cell growth and division,which in turn serve for the five pathways,that ultimately lead to an increased cancer growth and a decreased cell apoptosis.Based on the existing findings,this paper views cancer as a metabolic disease and urges for a better adjustment of cancer therapies.Cancer nutrition and metabolic modulation therapy should be and must be the main efforts for anticancer treatment.Due to the highly metabolic adaptive ability,cancer cell can rewire or shift to another metabolic pathway in face of harmful stress.Metabolic modulation therapy should therefore target different metabolic pathways.

关 键 词：肿瘤 有氧糖酵解 谷氨酰胺分解 一碳代谢 磷酸戊糖通路 脂肪酸从头合成 

分 类 号：R730.2[医药卫生—肿瘤]