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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癌症代谢：表型，信号传导和治疗靶标

异常代谢是癌症的主要标志。异常的癌症代谢，例如有氧糖酵解和合成代谢途径的增加，在肿瘤发生，转移，耐药和癌症干细胞中具有重要作用。众所周知的致癌信号转导途径，例如磷酸肌醇3-激酶（PI3K）/ AKT，Myc和Hippo途径，介导代谢基因的表达并增加代谢酶的活性。反之亦然，失调的代谢途径会导致细胞信号转导途径的缺陷，从而为不受限制的癌细胞增殖提供能量，构件和氧化还原电位。正在进行的研究和临床试验着重于通过小分子或饮食干预（例如，禁食，卡路里限制和间歇性禁食）抑制代谢酶。与遗传异质性相似，癌症的代谢表型具有高度异质性。这种异质性是由肿瘤微环境和遗传突变的各种线索导致的。因此，克服代谢可塑性是现代癌症治疗方法的重要目标。这篇综述重点介绍了有关癌症代谢表型的最新发现，并阐明了信号转导途径与代谢途径之间的相互作用。我们还为设计下一代癌症代谢药物提供了新颖的原理。这篇综述重点介绍了有关癌症代谢表型的最新发现，并阐明了信号转导途径与代谢途径之间的相互作用。我们还为设计下一代癌症代谢药物提供了新颖的原理。这篇综述重点介绍了有关癌症代谢表型的最新发现，并阐明了信号转导途径与代谢途径之间的相互作用。我们还为设计下一代癌症代谢药物提供了新颖的原理。