Department of Pathology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Department of Biology, Acadia University, Wolfville, NS B4P 2R6, Canada.
Int J Mol Sci. 2024 Apr 7;25(7):4102. doi: 10.3390/ijms25074102.
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/β-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.
癌症干细胞 (CSC) 是肿瘤中的一个亚群，由于其自我更新能力和对传统疗法的耐药性，促进了癌症的进展、转移和复发。CSC 特异性标记物和在 CSC 中高度活跃的信号通路已成为改善患者预后的有前途的策略。
本综述全面概述了各种癌症类型中实体瘤 CSC 相关的治疗靶点，包括关键的分子标记物醛脱氢酶、CD44、上皮细胞黏附分子和 CD133 以及信号通路，如 Wnt/β-catenin、Notch 和 Sonic Hedgehog。
我们讨论了广泛的治疗方式，包括靶向抗体、小分子抑制剂和近红外光免疫疗法，以及先进的遗传方法，如 RNA 干扰、CRISPR/Cas9 技术、适体、反义寡核苷酸、嵌合抗原受体 (CAR) T 细胞、CAR 自然杀伤细胞、双特异性 T 细胞衔接器、免疫毒素、抗体药物偶联物、治疗性肽和树突状细胞疫苗。
本综述涵盖了从临床前研究到正在进行的临床试验的发展，强调了基于 CSC 相关途径和分子的创新靶向策略，以克服治疗耐药性。我们旨在深入了解这些疗法在癌症治疗方面的潜力，强调在与癌症作斗争中需要采取多方面的方法。
这项全面的分析表明，CSC 领域的进展如何为新型靶向治疗方法的显著发展提供了信息，最终目标是使癌症患者获得更有效和持久的反应。
