Rahman Mahbuba, Hasan Mohammad Rubayet
Sidra Medical & Research Center, P.O. Box 26999 Doha, Qatar.
Weill Cornell Medical College in Qatar, P.O. Box 24144 Doha, Qatar.
Metabolites. 2015 Sep 30;5(4):571-600. doi: 10.3390/metabo5040571.
Metabolic alterations, driven by genetic and epigenetic factors, have long been known to be associated with the etiology of cancer. Furthermore, accumulating evidence suggest that cancer metabolism is intimately linked to drug resistance, which is currently one of the most important challenges in cancer treatment. Altered metabolic pathways help cancer cells to proliferate at a rate higher than normal, adapt to nutrient limited conditions, and develop drug resistance phenotypes. Application of systems biology, boosted by recent advancement of novel high-throughput technologies to obtain cancer-associated, transcriptomic, proteomic and metabolomic data, is expected to make a significant contribution to our understanding of metabolic properties related to malignancy. Indeed, despite being at a very early stage, quantitative data obtained from the omics platforms and through applications of (13)C metabolic flux analysis (MFA) in in vitro studies, researchers have already began to gain insight into the complex metabolic mechanisms of cancer, paving the way for selection of molecular targets for therapeutic interventions. In this review, we discuss some of the major findings associated with the metabolic pathways in cancer cells and also discuss new evidences and achievements on specific metabolic enzyme targets and target-directed small molecules that can potentially be used as anti-cancer drugs.
长期以来，人们一直认为由遗传和表观遗传因素驱动的代谢改变与癌症的病因有关。此外，越来越多的证据表明，癌症代谢与耐药性密切相关，而耐药性是目前癌症治疗中最重要的挑战之一。代谢途径的改变有助于癌细胞以高于正常的速度增殖，适应营养有限的条件，并产生耐药表型。随着新型高通量技术的最新进展，系统生物学的应用得以推动，从而获得与癌症相关的转录组学、蛋白质组学和代谢组学数据，这有望为我们理解与恶性肿瘤相关的代谢特性做出重大贡献。事实上，尽管仍处于非常早期的阶段，但从组学平台以及通过在体外研究中应用（13）C代谢通量分析（MFA）获得的定量数据，研究人员已经开始深入了解癌症复杂的代谢机制，为选择治疗干预的分子靶点铺平了道路。在这篇综述中，我们讨论了与癌细胞代谢途径相关的一些主要发现，还讨论了关于特定代谢酶靶点以及可能用作抗癌药物的靶向小分子的新证据和成就。
