Targeting cellular cholesterol for anticancer therapy
Targeting cellular cholesterol for anticancer therapy
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DOI：
10.1111/febs.15018
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发表时间：
2019-08-12
期刊：
影响因子：
5.4
通讯作者：
Kaur, Mandeep
中科院分区：
文献类型：
--
作者：
Gu, Liang;Saha, Sourav Taru;Kaur, Mandeep
癌细胞中的胆固醇代谢紊乱导致细胞内胆固醇积聚，从而产生耐药性，使这些细胞逃避凋亡信号过程，保持持续的细胞分裂和增殖。因此，降低癌细胞中的胆固醇被认为是一种潜在的抗癌策略。在这个方向上，已经提出了两种治疗策略：(A)抑制细胞内胆固醇的生物合成；(B)消耗癌细胞中多余的胆固醇。在这篇综述的第一阶段，我们整理了受胆固醇代谢紊乱干扰的癌症信号通路(特别是在乳腺癌中)，并强调了最近开发降胆固醇化合物的药物发现努力，其中一些目前正在进行临床试验。在第二阶段，基于对现有科学证据的分析，我们概念化并论证了过量胆固醇的耗尽可以使癌细胞对现有的治疗方法敏感，也可能有助于减轻癌症的耐药性。
Cholesterol dyshomeostasis in cancer cells leads to intracellular cholesterol accumulation, which imparts drug resistance and allows these cells to evade apoptotic signalling processes and maintain continuous cell division and proliferation. Therefore, cholesterol lowering in cancer cells has been envisaged as a potential anticancer strategy. In this direction, two therapeutic strategies have been proposed: (a) to inhibit the biosynthesis of cholesterol in the cells and (b) to deplete excess cholesterol from cancer cells. In the first phase of this review, we collate the cancer signalling pathways (particularly in breast cancer) that are perturbed by cholesterol dyshomeostasis and highlight recent drug discovery efforts to develop cholesterol-lowering compounds, some of which are currently under clinical trials. In the second phase, based on the analysis of the available scientific evidence, we conceptualize and argue that the depletion of excess cholesterol could sensitize cancer cells to available therapeutics and may also help to alleviate cancer drug resistance.