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靶向脂质合成代谢治疗以选择性消除癌症干细胞。

Therapeutic targeting of lipid synthesis metabolism for selective elimination of cancer stem cells.

机构信息

College of Pharmacy and Drug Information Research Institute, Sookmyung Women's University, Cheongparo 47-gil, Yongsan-gu, Seoul, 04310, Korea.

出版信息

Arch Pharm Res. 2019 Jan;42(1):25-39. doi: 10.1007/s12272-018-1098-z. Epub 2018 Dec 8.

Abstract

Cancer stem cells (CSCs) are believed to have an essential role in tumor resistance and metastasis; however, no therapeutic strategy for the selective elimination of CSCs has been established. Recently, several studies have shown that the metabolic regulation for ATP synthesis and biological building block generation in CSCs are different from that in bulk cancer cells and rather similar to that in normal tissue stem cells. To take advantage of this difference for CSC elimination therapy, many studies have tested the effect of blocking these metabolism. Two specific processes for lipid biosynthesis, i.e., fatty acid unsaturation and cholesterol biosynthesis, have been shown to be very effective and selective for CSC targets. In this review, lipid metabolism specific to CSCs are summarized. In addition, how monounsaturated fatty acid and cholesterol synthesis may contribute to CSC maintenance are discussed. Specifically, the molecular mechanism required for lipid synthesis and essential for stem cell biology is highlighted. The limit and preview of the lipid metabolism targeting for CSCs are also discussed.

摘要

癌症干细胞(CSCs)被认为在肿瘤耐药和转移中起关键作用;然而,目前尚无针对 CSCs 的选择性消除的治疗策略。最近,多项研究表明,CSCs 的 ATP 合成和生物砌块生成的代谢调节与大量癌细胞不同,而与正常组织干细胞相似。为了利用这种差异进行 CSC 消除治疗,许多研究已经测试了阻断这些代谢的效果。已经表明,两种特定的脂质生物合成过程,即脂肪酸不饱和和胆固醇生物合成,对 CSC 靶点非常有效和具有选择性。在这篇综述中,总结了 CSC 特有的脂质代谢。此外,还讨论了单不饱和脂肪酸和胆固醇合成如何有助于 CSC 的维持。特别强调了脂质合成所需的分子机制,这对干细胞生物学至关重要。还讨论了针对 CSCs 的脂质代谢的局限性和展望。

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