文章：

癌症中细胞信号传导与甲羟戊酸途径的相互作用

The interplay between cell signalling and the mevalonate pathway in cancer

原文发布日期：2016-08-26

DOI: 10.1038/nrc.2016.76

类型: Review Article

开放获取: 否

要点：

1. Mevalonate (MVA) pathway metabolites are essential for cancer cell survival and growth.
2. Expression of the genes encoding MVA pathway enzymes is controlled by the sterol regulatory element-binding protein (SREBP) family of transcription factors.
3. In cancer cells, oncogenic signalling pathways deregulate the activity of the SREBP transcription factors and MVA pathway enzymes.
4. Deregulated production of MVA pathway metabolites modulates multiple signalling pathways in cancer cells and contributes to transformation.
5. Clinical trials to evaluate the utility of MVA pathway inhibitors as anticancer agents have shown responses in some, but not all, patients; discovering biomarkers to identify responders and developing combination therapies will further enhance the utility of these inhibitors.
6. Inhibiting the SREBP transcription factors is a promising strategy to increase the efficacy of MVA pathway inhibitors as anticancer therapeutics, and also potentially to combat resistance to MVA pathway therapies.

要点翻译：

1. 甲羟酸途径代谢物对癌细胞的存活和生长至关重要。
2. 编码甲羟酸途径酶的基因表达受甾醇调节元件结合蛋白（SREBP）转录因子家族调控。
3. 在癌细胞中，致癌信号通路会破坏SREBP转录因子和甲羟酸途径酶的活性调节。
4. 甲羟酸途径代谢物的失调产生会调节癌细胞中的多种信号通路，并促进细胞转化。
5. 评估甲羟酸途径抑制剂作为抗癌药物效用的临床试验显示，部分患者产生应答，但并非全部患者；发现识别应答者的生物标志物并开发联合疗法将进一步提高这些抑制剂的效用。
6. 抑制SREBP转录因子是一种有前景的策略，可提高甲羟酸途径抑制剂作为抗癌疗法的疗效，并可能潜在对抗甲羟酸途径疗法的耐药性。

英文摘要：

The mevalonate (MVA) pathway is an essential metabolic pathway that uses acetyl-CoA to produce sterols and isoprenoids that are integral to tumour growth and progression. In recent years, many oncogenic signalling pathways have been shown to increase the activity and/or the expression of MVA pathway enzymes. This Review summarizes recent advances and discusses unique opportunities for immediately targeting this metabolic vulnerability in cancer with agents that have been approved for other therapeutic uses, such as the statin family of drugs, to improve outcomes for cancer patients.

摘要翻译： 

甲羟戊酸（MVA）途径是一条重要的代谢通路，它利用乙酰辅酶A生成甾醇和类异戊二烯，这些产物对肿瘤的生长和进展至关重要。近年来，许多致癌信号通路已被证实可提高MVA途径酶的活性和/或表达。本综述总结了最新进展，并探讨了利用已获批用于其他治疗用途的药物（如他汀类药物）立即靶向这一癌症代谢脆弱性的独特机会，以改善癌症患者的治疗效果。

原文链接：

The interplay between cell signalling and the mevalonate pathway in cancer