Targeting cancer metabolism in the era of precision oncology.
Targeting cancer metabolism in the era of precision oncology.
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DOI：
10.1038/s41573-021-00339-6
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Dang CV
中科院分区：
文献类型：
--
作者：
Stine ZE;Schug ZT;Salvino JM;Dang CV
自从瓦尔堡发现癌症代谢的改变以来，已经过去了100年，自从西德尼·法伯引入抗叶酸药物改变了儿童白血病的治疗方法以来，已经过去了70多年，自从代谢与致癌基因有关以来，已经过去了20年。然而，在过去的十年中，靶向癌症代谢治疗的进展有限。只有少数基于代谢的癌症药物已经成功开发，其中一些正在进行临床试验或正在进行临床试验。靶向癌细胞内在代谢的策略通常没有考虑到非癌基质细胞和免疫细胞的代谢，这些细胞在肿瘤进展和维持中起关键作用。通过考虑免疫细胞代谢和先天性代谢异常的临床表现，有可能在代谢药物的开发过程中分离出不良的肿瘤外、靶向效应。因此，药物设计的概念框架必须考虑肿瘤免疫微环境中非癌细胞以及癌细胞的代谢脆弱性。在这篇评论中，我们涵盖了靶向癌症代谢的最新进展，显着的里程碑和挫折，并讨论了该领域的前进方向。尽管代谢和致癌基因之间存在联系，但很少有基于代谢的癌症药物被成功开发出来。本综述涵盖了靶向癌症代谢的挫折和最新进展，并讨论了该领域的前进道路。
One hundred years have passed since Warburg discovered alterations in cancer metabolism, more than 70 years since Sidney Farber introduced anti-folates that transformed the treatment of childhood leukaemia, and 20 years since metabolism was linked to oncogenes. However, progress in targeting cancer metabolism therapeutically in the past decade has been limited. Only a few metabolism-based drugs for cancer have been successfully developed, some of which are in — or en route to — clinical trials. Strategies for targeting the intrinsic metabolism of cancer cells often did not account for the metabolism of non-cancer stromal and immune cells, which have pivotal roles in tumour progression and maintenance. By considering immune cell metabolism and the clinical manifestations of inborn errors of metabolism, it may be possible to isolate undesirable off-tumour, on-target effects of metabolic drugs during their development. Hence, the conceptual framework for drug design must consider the metabolic vulnerabilities of non-cancer cells in the tumour immune microenvironment, as well as those of cancer cells. In this Review, we cover the recent developments, notable milestones and setbacks in targeting cancer metabolism, and discuss the way forward for the field. Despite the link between metabolism and oncogenes, very few metabolism-based drugs for cancer have been successfully developed. This Review covers the setbacks and recent developments in targeting cancer metabolism, and discusses the path forward for the field.
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影响因子：
5.2
作者：
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影响因子：
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64.8
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Zhou M
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82.9
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通讯作者：
Krummel MF