Cancer metabolism: a therapeutic perspective

被引:1020
作者
Martinez-Outschoorn, Ubaldo E. [1 ]
Peiris-Pages, Maria [2 ,3 ]
Pestell, Richard G. [1 ]
Sotgia, Federica [2 ,3 ,4 ]
Lisanti, Michael P. [2 ,3 ]
机构
[1] Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, 233 South 10th St, Philadelphia, PA 19107 USA
[2] Univ Manchester, Canc Res UK Manchester Inst, Breast Canc Now Manchester Res Unit, Inst Canc Sci, Paterson Bldg,Wilmslow Rd, Manchester M20 4BX, Lancs, England
[3] Univ Manchester, Canc Res UK Manchester Inst, Inst Canc Sci, MCCM, Paterson Bldg,Wilmslow Rd, Manchester M20 4BX, Lancs, England
[4] Univ Salford, Sch Environm & Life Sci, Cockcroft Bldg, Salford M5 4WT, Lancs, England
基金
美国国家卫生研究院; 欧洲研究理事会;
关键词
TUMOR-CELL SURVIVAL; SMALL-MOLECULE INHIBITORS; INDUCIBLE FACTOR-I; ATP CITRATE LYASE; OXIDATIVE STRESS; MITOCHONDRIAL BIOGENESIS; PHASE-I; LACTATE-DEHYDROGENASE; AEROBIC GLYCOLYSIS; PANCREATIC-CANCER;
D O I
10.1038/nrclinonc.2016.60
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Awareness that the metabolic phenotype of cells within tumours is heterogeneous and distinct from that of their normal counterparts is growing. In general, tumour cells metabolize glucose, lactate, pyruvate, hydroxybutyrate, acetate, glutamine, and fatty acids at much higher rates than their nontumour equivalents; however, the metabolic ecology of tumours is complex because they contain multiple metabolic compartments, which are linked by the transfer of these catabolites. This metabolic variability and flexibility enables tumour cells to generate ATP as an energy source, while maintaining the reduction-oxidation (redox) balance and committing resources to biosynthesis processes that are essential for cell survival, growth, and proliferation. Importantly, experimental evidence indicates that metabolic coupling between cell populations with different, complementary metabolic profiles can induce cancer progression. Thus, targeting the metabolic differences between tumour and normal cells holds promise as a novel anticancer strategy. In this Review, we discuss how cancer cells reprogramme their metabolism and that of other cells within the tumour microenvironment in order to survive and propagate, thus driving disease progression; in particular, we highlight potential metabolic vulnerabilities that might be targeted therapeutically.
引用
收藏
页码:11 / 31
页数:21
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