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受实体瘤癌症干细胞启发:靶向促肿瘤因子与信号通路的治疗进展

英文原题:Informed by Cancer Stem Cells of Solid Tumors: Advances in Treatments Targeting Tumor-Promoting Factors and Pathways.

PubMed 2024/04/07(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

研究概要

肿瘤干细胞(CSCs)是肿瘤内的一类亚群,因其自我更新能力及对常规治疗的耐药性而促进肿瘤进展、转移和复发。

中文摘要

癌症干细胞(CSC)是肿瘤中的一个亚群,因具有自我更新能力且对常规治疗耐药,可促进癌症进展、转移和复发。靶向CSC特异性标志物及其高度活跃的信号通路,已成为改善患者结局的有前景策略。本文全面综述多种实体瘤中与CSC相关的治疗靶点,包括醛脱氢酶、CD44、上皮细胞黏附分子和CD133等关键分子标志物,以及Wnt/β-catenin、Notch和Sonic Hedgehog等信号通路。我们讨论多种治疗方式,包括靶向抗体、小分子抑制剂、近红外光免疫疗法,以及RNA干扰、CRISPR/Cas9技术、适配体、反义寡核苷酸、嵌合抗原受体(CAR)T细胞、CARNK 细胞、双特异性T细胞衔接器、免疫毒素、药物-抗体偶联物、治疗性肽和树突状细胞疫苗等先进基因和免疫治疗方法。本文涵盖从临床前研究到正在进行的临床试验的进展,突出基于CSC相关通路和分子开发的创新靶向策略,以克服治疗耐药。我们旨在探讨这些疗法改变癌症治疗的潜力,并强调抗癌需要多方面综合策略。综述分析显示,CSC领域的进展已推动新型靶向治疗方法的重要发展,最终目标是让癌症患者获得更有效且更持久的应答。

展开英文摘要原文

Cancer stem cells (CSCs) represent a subpopulation within tumors that promote cancer progression, metastasis, and recurrence due to their self-renewal capacity and resistance to conventional therapies. CSC-specific markers and signaling pathways highly active in CSCs have emerged as a promising strategy for improving patient outcomes. This review provides a comprehensive overview of the therapeutic targets associated with CSCs of solid tumors across various cancer types, including key molecular markers aldehyde dehydrogenases, CD44, epithelial cellular adhesion molecule, and CD133 and signaling pathways such as Wnt/ -catenin, Notch, and Sonic Hedgehog. We discuss a wide array of therapeutic modalities ranging from targeted antibodies, small molecule inhibitors, and near-infrared photoimmunotherapy to advanced genetic approaches like RNA interference, CRISPR/Cas9 technology, aptamers, antisense oligonucleotides, chimeric antigen receptor (CAR) T cells, CAR natural killer cells, bispecific T cell engagers, immunotoxins, drug-antibody conjugates, therapeutic peptides, and dendritic cell vaccines. This review spans developments from preclinical investigations to ongoing clinical trials, highlighting the innovative targeting strategies that have been informed by CSC-associated pathways and molecules to overcome therapeutic resistance. We aim to provide insights into the potential of these therapies to revolutionize cancer treatment, underscoring the critical need for a multi-faceted approach in the battle against cancer. This comprehensive analysis demonstrates how advances made in the CSC field have informed significant developments in novel targeted therapeutic approaches, with the ultimate goal of achieving more effective and durable responses in cancer patients.

论文信息

作者
MacLean MR、Walker OL、Arun RP、Fernando W、Marcato P
单位
Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada.Canada
文献类型
综述
期刊
International journal of molecular sciences2024 Apr 7
原文标识
PubMed 38612911 · DOI 10.3390/ijms25074102