Targeting the Achilles’ heel of cancer stem cells

Advances in understanding tumor cell heterogeneity and plasticity have led to increasing acceptance of the CSCs hypothesis. CSCs, a subset of cells with self-renewal and high plasticity, play critical roles in tumor initiation, metastasis, drug resistance, recurrence, and the establishment of immunosuppressive microenvironments. Recent studies have unveiled the complex regulation mechanisms underlying the interactions between CSCs and cells within the TME. The remodeling and mutual interactions between CSCs and their niche, as well as the CSCs-targeted therapeutic strategies, have now become frontiers in CSCs biology research. In this review, we summarize current advances in CSCs biology, focusing on their fundamental characteristics and key functions, their dynamic interactions with and remodeling of the TME, as well as therapeutic interventions targeting CSCs and their regulatory niche.