文章：

多胺代谢与癌症：治疗、挑战和机遇

Polyamine metabolism and cancer: treatments, challenges and opportunities

原文发布日期：2018-09-04

DOI: 10.1038/s41568-018-0050-3

类型: Review Article

开放获取: 否

英文摘要：

Advances in our understanding of the metabolism and molecular functions of polyamines and their alterations in cancer have led to resurgence in the interest of targeting polyamine metabolism as an anticancer strategy. Increasing knowledge of the interplay between polyamine metabolism and other cancer-driving pathways, including the PTEN–PI3K–mTOR complex 1 (mTORC1), WNT signalling and RAS pathways, suggests potential combination therapies that will have considerable clinical promise. Additionally, an expanding number of promising clinical trials with agents targeting polyamines for both therapy and prevention are ongoing. New insights into molecular mechanisms linking dysregulated polyamine catabolism and carcinogenesis suggest additional strategies that can be used for cancer prevention in at-risk individuals. In addition, polyamine blocking therapy, a strategy that combines the inhibition of polyamine biosynthesis with the simultaneous blockade of polyamine transport, can be more effective than therapies based on polyamine depletion alone and may involve an antitumour immune response. These findings open up new avenues of research into exploiting aberrant polyamine metabolism for anticancer therapy.

摘要翻译： 

多胺代谢及其分子功能的研究进展，以及对其在癌症中变化的认识，促使针对多胺代谢的抗癌策略再度引起关注。对多胺代谢与其他癌症驱动通路（包括PTEN–PI3K–mTOR复合物1、WNT信号传导和RAS通路）之间相互作用日益深入的了解，提示了具有重要临床前景的潜在联合疗法。此外，针对多胺的治疗和预防药物的临床试验数量不断增加，且前景广阔。对多胺分解代谢失调与致癌作用之间联系的分子机制的新见解，提出了可用于高危个体癌症预防的其他策略。另外，多胺阻断疗法——一种同时抑制多胺生物合成和阻断多胺转运的策略——可能比单纯基于多胺耗竭的疗法更有效，并可能涉及抗肿瘤免疫反应。这些发现为利用异常多胺代谢进行抗癌治疗开辟了新的研究途径。

原文链接：

Polyamine metabolism and cancer: treatments, challenges and opportunities