Background

Cancer cells rewire their metabolism to meet the energetic and biosynthetic demands of their high proliferation rates and environment. Metabolic reprogramming of cancer cells may result in strong dependencies on nutrients that could be exploited for therapy. While these dependencies may be in part due to the nutrient environment of tumors, mutations or expression changes in metabolic genes also reprogram metabolic pathways and create addictions to extracellular nutrients.

Scope of review

This review summarizes the major nutrient dependencies of cancer cells focusing on their discovery and potential mechanisms by which metabolites become limiting for tumor growth. We further detail available therapeutic interventions based on these metabolic features and highlight opportunities for restricting nutrient availability as an anti-cancer strategy.

Major conclusions

Strategies to limit nutrients required for tumor growth using dietary interventions or nutrient degrading enzymes have previously been suggested for cancer therapy. The best clinical example of exploiting cancer nutrient dependencies is the treatment of leukemia with l-asparaginase, a first-line chemotherapeutic that depletes serum asparagine. Despite the success of nutrient starvation in blood cancers, it remains unclear whether this approach could be extended to other solid tumors. Systematic studies to identify nutrient dependencies unique to individual tumor types have the potential to discover targets for therapy.

中文翻译：

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针对癌细胞的细胞外营养依赖性。

背景

癌细胞重新调整其新陈代谢，以满足其高增殖率和环境对能量和生物合成的需求。癌细胞的代谢重编程可能导致对营养物的强烈依赖性，而营养物可以用于治疗。尽管这些依赖性可能部分归因于肿瘤的营养环境，但是代谢基因的突变或表达变化也重新编程了代谢途径，并引起了细胞外营养的成瘾。

审查范围

这篇综述总结了癌细胞的主要营养依赖性，重点是癌细胞的发现和可能的代谢物代谢机制，这些代谢物成为限制肿瘤生长的潜在机制。我们基于这些代谢特征进一步详细介绍了可用的治疗干预措施，并着重指出了限制营养供应的机会，以此作为一种抗癌策略。

主要结论

先前已经提出了通过饮食干预或营养降解酶限制肿瘤生长所需营养的策略，用于癌症治疗。利用癌症营养素依赖性的最好的临床例子是用l-天冬酰胺酶治疗白血病，l-天冬酰胺酶是一种消耗血清天冬酰胺的一线化学疗法。尽管营养缺乏症在血液癌症中取得了成功，但尚不清楚这种方法是否可以扩展到其他实体瘤。识别每种肿瘤类型所特有的营养依赖性的系统研究有可能发现治疗靶标。