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癌症干细胞:获取、特征、治疗意义、靶向策略和未来前景。

Cancer Stem Cells: Acquisition, Characteristics, Therapeutic Implications, Targeting Strategies and Future Prospects.

机构信息

Amity Institute of Biotechnology, Amity University, Mumbai-Pune Expressway, Bhatan, Panvel, Mumbai, Maharashtra, 410206, India.

出版信息

Stem Cell Rev Rep. 2019 Jun;15(3):331-355. doi: 10.1007/s12015-019-09887-2.

Abstract

Since last two decades, the major cancer research has focused on understanding the characteristic properties and mechanism of formation of Cancer stem cells (CSCs), due to their ability to initiate tumor growth, self-renewal property and multi-drug resistance. The discovery of the mechanism of acquisition of stem-like properties by carcinoma cells via epithelial-mesenchymal transition (EMT) has paved a way towards a deeper understanding of CSCs and presented a possible avenue for the development of therapeutic strategies. In spite of years of research, various challenges, such as identification of CSC subpopulation, lack of appropriate experimental models, targeting cancer cells and CSCs specifically without harming normal cells, are being faced while dealing with CSCs. Here, we discuss the biology and characteristics of CSCs, mode of acquisition of stemness (via EMT) and development of multi-drug resistance, the role of tumor niche, the process of dissemination and metastasis, therapeutic implications of CSCs and necessity of targeting them. We emphasise various strategies being developed to specifically target CSCs, including those targeting biomarkers, key pathways and microenvironment. Finally, we focus on the challenges that need to be subdued and propose the aspects that need to be addressed in future studies in order to broaden the understanding of CSCs and develop novel strategies to eradicate them in clinical applications. Graphical Abstract Cancer Stem Cells(CSCs) have gained much attention in the last few decades due to their ability to initiate tumor growth and, self-renewal property and multi-drug resistance. Here, we represent the CSC model of cancer, Characteristics of CSCs, acquisition of stemness and metastatic dissemination of cancer, Therapeutic implications of CSCs and Various strategies being employed to target and eradicate CSCs.

摘要

在过去的二十年中,由于癌症干细胞 (CSC) 能够启动肿瘤生长、自我更新特性和多药耐药性,主要的癌症研究集中在理解其特征特性和形成机制上。通过上皮-间充质转化 (EMT) 获得类似干细胞特性的癌细胞的机制的发现,为深入了解 CSCs 铺平了道路,并为开发治疗策略提供了可能的途径。尽管经过多年的研究,但在处理 CSCs 时,仍然面临着各种挑战,例如鉴定 CSC 亚群、缺乏适当的实验模型、特异性靶向癌细胞和 CSCs 而不伤害正常细胞等。在这里,我们讨论了 CSCs 的生物学和特性、获得干性(通过 EMT)和多药耐药性的模式、肿瘤生态位的作用、播散和转移的过程、CSCs 的治疗意义以及靶向它们的必要性。我们强调了正在开发的各种特异性靶向 CSCs 的策略,包括靶向生物标志物、关键途径和微环境的策略。最后,我们关注需要克服的挑战,并提出未来研究中需要解决的方面,以扩大对 CSCs 的理解并开发在临床应用中根除它们的新策略。

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