摘要
癌相关成纤维细胞(CAF)在几种癌症类型的发展过程中是活化的成纤维细胞,因此成为癌症治疗的有吸引力的治疗靶标。 PT-100和阻断CAF功能的sibrotuzumab等药物已经进入临床试验阶段。然而,这些药物在患者中表现出有限的功效,部分归因于目前使用的用于确定功效的生物标志物不是CAF特异性的事实。此外,CAF的消耗可能通过诱导免疫抑制和缺氧促进癌发生并加速癌症进展,导致生存降低。越来越多的证据表明,通过靶向不同的信号传导途径和代谢机制,恢复关键microRNA的表达诱导CAF功能性转化为正常成纤维细胞。因此,通过改变microRNA的特异性表达,而非靶向消融,将CAF重编程为正常成纤维细胞可能是用于癌症治疗的有效的新策略。本综述重点介绍了CAFs转化过程中涉及的特定microRNAs及其在肿瘤发生和化疗耐药过程中的多重作用。
关键词: 癌相关成纤维细胞,microRNA,重编程,信号传导途径,代谢途径,靶向治疗。
Current Molecular Medicine
Title:Reprograming Carcinoma Associated Fibroblasts by microRNAs
Volume: 17 Issue: 5
关键词: 癌相关成纤维细胞,microRNA,重编程,信号传导途径,代谢途径,靶向治疗。
摘要: Carcinoma-associated fibroblasts (CAFs) are activated fibroblasts during development of several cancer types, and therefore emerge as an attractive therapeutic target for cancer therapy. Drugs such as PT-100 and sibrotuzumab that block the functions of CAFs have already been in clinical trials. However, these drugs exhibit limited efficacy in patients, partially due to the fact that currently used biomarkers for determining efficacy are not CAF-specific. Furthermore, depletion of CAFs may promote carcinogenesis and accelerate cancer progression by inducing immunosuppression and hypoxia, leading to reduced survival. Accumulating evidence demonstrates that restoring the expression of key microRNA induces the functional conversion of CAFs into normal fibroblasts by targeting different signaling pathways and metabolic mechanisms. Therefore, reprograming CAFs into normal fibroblasts by altering specific expression of microRNAs, rather than targeted ablation, may be an effective, novel strategy for cancer treatment. This review focuses on specific microRNAs involved in the transformation of CAFs as well as their multiple roles during tumorigenesis and chemo-resistance.
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Reprograming Carcinoma Associated Fibroblasts by microRNAs, Current Molecular Medicine 2017; 17 (5) . https://dx.doi.org/10.2174/1566524018666171205113959
DOI https://dx.doi.org/10.2174/1566524018666171205113959 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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