Cancer stem cells: Bridging microenvironmental interactions and clinical therapy

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.