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癌症干细胞中的调控和信号通路:对癌症靶向治疗的启示。

Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.

机构信息

Laboratory of Aging Research and Cancer Agent Target, State Key Laboratory of Biotherapy, Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, P.R. China.

Department of Pediatric Nephrology Nursing, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, P.R. China.

出版信息

Mol Cancer. 2023 Oct 18;22(1):172. doi: 10.1186/s12943-023-01877-w.

Abstract

Cancer stem cells (CSCs), initially identified in leukemia in 1994, constitute a distinct subset of tumor cells characterized by surface markers such as CD133, CD44, and ALDH. Their behavior is regulated through a complex interplay of networks, including transcriptional, post-transcriptional, epigenetic, tumor microenvironment (TME), and epithelial-mesenchymal transition (EMT) factors. Numerous signaling pathways were found to be involved in the regulatory network of CSCs. The maintenance of CSC characteristics plays a pivotal role in driving CSC-associated tumor metastasis and conferring resistance to therapy. Consequently, CSCs have emerged as promising targets in cancer treatment. To date, researchers have developed several anticancer agents tailored to specifically target CSCs, with some of these treatment strategies currently undergoing preclinical or clinical trials. In this review, we outline the origin and biological characteristics of CSCs, explore the regulatory networks governing CSCs, discuss the signaling pathways implicated in these networks, and investigate the influential factors contributing to therapy resistance in CSCs. Finally, we offer insights into preclinical and clinical agents designed to eliminate CSCs.

摘要

癌症干细胞(CSCs)于 1994 年在白血病中首次被发现,是肿瘤细胞的一个独特亚群,其特征是表面标志物如 CD133、CD44 和 ALDH。它们的行为受到转录、转录后、表观遗传、肿瘤微环境(TME)和上皮-间充质转化(EMT)因子等网络的复杂相互作用的调节。许多信号通路被发现参与了 CSCs 的调控网络。CSC 特征的维持在驱动 CSC 相关肿瘤转移和赋予治疗耐药性方面起着关键作用。因此,CSCs 已成为癌症治疗的有前途的靶点。迄今为止,研究人员已经开发了几种针对 CSCs 的抗癌药物,其中一些治疗策略正在进行临床前或临床试验。在这篇综述中,我们概述了 CSCs 的起源和生物学特征,探讨了调控 CSCs 的调控网络,讨论了这些网络中涉及的信号通路,并研究了导致 CSCs 治疗耐药性的影响因素。最后,我们深入探讨了旨在消除 CSCs 的临床前和临床制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f236/10583419/b5aa9147eede/12943_2023_1877_Fig1_HTML.jpg

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