文章：

靶向代谢转化用于癌症治疗

Targeting metabolic transformation for cancer therapy

原文发布日期：2010-03-19

DOI: 10.1038/nrc2817

类型: Review Article

开放获取: 否

要点：

1. The metabolism observed in tumours is different from that of the normal tissues from which the tumours are derived. This altered metabolic phenotype allows cancer cells to accommodate increased metabolic demands and adapt to environmental changes.
2. Specific alterations in metabolic pathways may generate opportunities to design new therapeutic approaches.
3. Metabolic alterations in cancer can be driven by changes in signalling pathways involving kinases such as PI3K and mTOR, and transcription factors, including hypoxia inducible factor and MYC. These are important targets for cancer therapy in general and cancer metabolism in particular.
4. Cancer cells increase their rate of glucose and glutamine metabolism for bioenergetic and anabolic purposes. These important external carbon sources are diverted to generate DNA, proteins and lipids that are required for cancer cell growth.
5. Cancer-specific isoforms of enzymes involved in energy metabolism, anabolism and adaptation to low oxygen may be new druggable targets for cancer therapy with potentially improved therapeutic indices compared with current therapy.

要点翻译：

1. 肿瘤中观察到的代谢与衍生肿瘤的正常组织不同。这种改变的代谢表型使癌细胞能够适应增加的代谢需求并应对环境变化。
2. 代谢通路的具体改变可能为设计新的治疗方法创造机会。
3. 癌症中的代谢改变可由涉及激酶（如PI3K和mTOR）和转录因子（包括缺氧诱导因子和MYC）的信号通路变化驱动。这些是癌症治疗尤其是癌症代谢领域的重要靶点。
4. 癌细胞提高葡萄糖和谷氨酰胺的代谢速率以满足生物能量和合成代谢需求。这些重要的外部碳源被转而用于生成癌细胞生长所需的DNA、蛋白质和脂质。
5. 参与能量代谢、合成代谢及低氧适应的癌症特异性酶亚型，可能成为癌症治疗的新药物靶点，与现有疗法相比有望获得更佳的治疗指数。

英文摘要：

Cancer therapy has long relied on the rapid proliferation of tumour cells for effective treatment. However, the lack of specificity in this approach often leads to undesirable side effects. Many reports have described various 'metabolic transformation' events that enable cancer cells to survive, suggesting that metabolic pathways might be good targets. There are currently several drugs under development or in clinical trials that are based on specifically targeting the altered metabolic pathways of tumours. This Review highlights pathways against which there are already drugs in different stages of development and also discusses additional druggable targets.

摘要翻译： 

长期以来，癌症治疗依赖于肿瘤细胞的快速增殖来实现疗效。然而，这种方法缺乏特异性，往往导致不良副作用。许多研究描述了多种使癌细胞得以存活的“代谢转化”事件，提示代谢通路可能是良好的靶点。目前已有若干药物正在开发或临床试验阶段，其基础正是特异性靶向肿瘤发生改变的代谢通路。本综述重点介绍了已有药物处于不同开发阶段的通路，并讨论了其他可成药的靶点。

原文链接：

Targeting metabolic transformation for cancer therapy