Hirschey Matthew D, DeBerardinis Ralph J, Diehl Anna Mae E, Drew Janice E, Frezza Christian, Green Michelle F, Jones Lee W, Ko Young H, Le Anne, Lea Michael A, Locasale Jason W, Longo Valter D, Lyssiotis Costas A, McDonnell Eoin, Mehrmohamadi Mahya, Michelotti Gregory, Muralidhar Vinayak, Murphy Michael P, Pedersen Peter L, Poore Brad, Raffaghello Lizzia, Rathmell Jeffrey C, Sivanand Sharanya, Vander Heiden Matthew G, Wellen Kathryn E
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC 27701, USA; Department of Pharmacology & Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Children's Medical Center Research Institute, University of Texas - Southwestern Medical Center, Dallas, TX 75390, USA.
Semin Cancer Biol. 2015 Dec;35 Suppl:S129-S150. doi: 10.1016/j.semcancer.2015.10.002. Epub 2015 Oct 8.
Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review "Hallmarks of Cancer", where dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results demonstrate that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it.
癌症是一种以细胞无节制增殖为特征的疾病。为了维持生长,癌细胞会经历复杂的代谢重排,其特征是参与能量产生和生物合成过程的代谢途径发生变化。癌细胞的代谢转变的相关性最近已被纳入更新版的《癌症的特征》综述中,其中细胞代谢失调被列为一个新出现的特征。虽然有几条证据表明代谢重编程是由癌基因和肿瘤抑制基因的协同作用所编排的,但在某些情况下,改变的代谢可以在肿瘤发生中起主要作用。最近,参与关键代谢途径的胞质和线粒体酶的突变已与遗传性和散发性癌症形式相关联。总之,这些结果表明,异常代谢,曾经仅仅被视为致癌重编程的一种附带现象,在肿瘤发生中起着关键作用,能够控制细胞中的遗传和表观遗传事件。在本综述中,作为确定广泛治疗方法的更大努力的一部分,我们讨论了代谢与癌症之间的关系。我们关注营养代谢的主要改变以及代谢与表观遗传学之间新出现的联系。最后,我们讨论了在癌症中操纵代谢的潜在策略以及应考虑的权衡。对癌症中一系列代谢改变的更多研究有可能发现治疗癌症的新方法。