Cancer Stem Cells in Drug Delivery Strategies: Current Advances and Future Directions.
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Cancer Stem Cells (CSCs) are scarce within tumors, yet they are implicated in tumor initiation, disease progression, treatment failure, and relapse. Thus, presenting a distinct therapeutic challenge. This review examines how CSCs are defined and identified and how delivery systems have been adapted to reach or disable them, with particular attention to childhood malignancies. We distinguish evolutionary, hierarchical, and dynamic hierarchical accounts of CSC propagation before discussing marker expression, metabolic flexibility, and altered signaling. The therapeutic literature is organized into five areas: combination treatment, direct delivery to CSCs, manipulation of the CSC niche, biomimetic carriers, and immune-based targeting. The practical strengths and limitations of each approach are evaluated. We also consider rational combinations and the obstacles that continue to impede clinical translation. Aligning carrier design more closely with CSC biology may enable durable tumor control and more individualized treatment.