Cancer Metabolism: Phenotype, Signaling and Therapeutic Targets.
Cancer Metabolism: Phenotype, Signaling and Therapeutic Targets.
复制标题
癌症代谢：表型、信号传导和治疗靶点。
作者：
Park JH;Pyun WY;Park HW
新陈代谢异常是癌症的一个主要标志。肿瘤代谢异常，如有氧糖酵解和合成代谢途径增加，在肿瘤的发生、转移、耐药和肿瘤干细胞等方面起着重要作用。众所周知的致癌信号通路，如磷脂酰肌醇3-激酶(PI3K)/AKT、Myc和Hippo途径，可以调节代谢基因的表达，增加代谢酶的活性。反之亦然，去调控的代谢途径导致细胞信号转导途径的缺陷，而细胞信号转导途径又为癌细胞不受抑制的增殖提供能量、构件和氧化还原潜力。正在进行研究和临床试验，重点是小分子或饮食干预(例如，禁食、卡路里限制和间歇性禁食)对代谢酶的抑制。与遗传异质性相似，癌症的代谢表型也是高度异质性的。这种异质性是由肿瘤微环境和基因突变的不同线索造成的。因此，克服代谢可塑性是现代癌症治疗的重要目标。这篇综述重点介绍了最近在癌症代谢表型方面的发现，并阐明了信号转导通路和代谢通路之间的相互作用。我们还为设计下一代癌症代谢药物提供了新的理论基础。
Aberrant metabolism is a major hallmark of cancer. Abnormal cancer metabolism, such as aerobic glycolysis and increased anabolic pathways, has important roles in tumorigenesis, metastasis, drug resistance, and cancer stem cells. Well-known oncogenic signaling pathways, such as phosphoinositide 3-kinase (PI3K)/AKT, Myc, and Hippo pathway, mediate metabolic gene expression and increase metabolic enzyme activities. Vice versa, deregulated metabolic pathways contribute to defects in cellular signal transduction pathways, which in turn provide energy, building blocks, and redox potentials for unrestrained cancer cell proliferation. Studies and clinical trials are being performed that focus on the inhibition of metabolic enzymes by small molecules or dietary interventions (e.g., fasting, calorie restriction, and intermittent fasting). Similar to genetic heterogeneity, the metabolic phenotypes of cancers are highly heterogeneous. This heterogeneity results from diverse cues in the tumor microenvironment and genetic mutations. Hence, overcoming metabolic plasticity is an important goal of modern cancer therapeutics. This review highlights recent findings on the metabolic phenotypes of cancer and elucidates the interactions between signal transduction pathways and metabolic pathways. We also provide novel rationales for designing the next-generation cancer metabolism drugs.
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影响因子：
11.2
作者：
Beloueche-Babari M;Wantuch S;Casals Galobart T;Koniordou M;Parkes HG;Arunan V;Chung YL;Eykyn TR;Smith PD;Leach MO
通讯作者：
Leach MO
影响因子：
8.8
作者：
Benjamin, Don;Robay, Dimitri;Hall, Michael N.
通讯作者：
Hall, Michael N.
影响因子：
64.8
作者：
COLLINS, S;GROUDINE, M
通讯作者：
GROUDINE, M
影响因子：
11.4
作者：
Bouchard, C;Marquardt, J;Eilers, M
通讯作者：
Eilers, M
影响因子：
3.7
作者：
Barbano, Raffaela;Muscarella, Lucia Anna;Parrella, Paola
通讯作者：
Parrella, Paola