Wang Huiling, Li Junshu, Du Fei, Deng Hongxin
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Clin Transl Med. 2025 Jul;15(7):e70406. doi: 10.1002/ctm2.70406.
Cancer stem cells (CSCs) are a core subpopulation of tumour tissues exhibiting stem cell properties. Although they constitute only a minority of tumour cells, CSCs have become a central force driving tumourigenesis, metastasis, recurrence and resistance to therapy, owing to their abilities for self-renewal, multi-lineage differentiation and tumour-initiating ability. Recent advances in multi-omics analysis, lineage tracing and single-cell sequencing technologies have systematically elucidated the dynamic biology of CSCs, including their epigenetic plasticity, metabolic adaptations and phenotypic heterogeneity, which depend on their ecological niche. In this review, we summarise the biological properties of CSCs, the molecular regulatory mechanisms and the complex interactions with the tumour microenvironment. We focus on strategies to target CSCs and the clinical translational challenges associated with these approaches. Collectively, this review organically integrates basic mechanisms and clinical translational research on CSCs, offering a comprehensive framework for understanding tumour biology and developing precision therapeutic strategies. HIGHLIGHTS: Systems integration of CSC biology: Elucidate the dynamic properties, self-renewal, plasticity and drug resistance. Microenvironmental interactions: Bidirectional interactions between CSCs and other cells, providing insights into niche-driven immune evasion and metastasis. Therapeutic strategies: Evaluate emerging therapies targeting CSC-specific markers and signals. Future directions: Challenges are discussed, with proposed solutions including multi-omics-guided precision medicine and microenvironment remodelling.
癌症干细胞（CSCs）是肿瘤组织中具有干细胞特性的核心亚群。尽管它们仅占肿瘤细胞的少数，但由于其自我更新、多谱系分化和肿瘤起始能力，CSCs已成为驱动肿瘤发生、转移、复发和治疗抵抗的核心力量。多组学分析、谱系追踪和单细胞测序技术的最新进展系统地阐明了CSCs的动态生物学特性，包括其表观遗传可塑性、代谢适应性和表型异质性，这些特性取决于它们的生态位。在本综述中，我们总结了CSCs的生物学特性、分子调控机制以及与肿瘤微环境的复杂相互作用。我们重点关注靶向CSCs的策略以及与这些方法相关的临床转化挑战。总体而言，本综述有机地整合了CSCs的基本机制和临床转化研究，为理解肿瘤生物学和制定精准治疗策略提供了一个全面的框架。要点：CSC生物学的系统整合：阐明动态特性、自我更新、可塑性和耐药性。微环境相互作用：CSCs与其他细胞之间的双向相互作用，为生态位驱动的免疫逃逸和转移提供见解。治疗策略：评估针对CSC特异性标志物和信号的新兴疗法。未来方向：讨论挑战，提出的解决方案包括多组学指导的精准医学和微环境重塑。
