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Cancer relapse is one of the major setbacks in pediatric oncology. Cancer stem cells (CSCs) have emerged as a major driving force governing tumor recurrence. CSCs are a small subpopulation of cells capable of regenerating a tumor and are resistant to conventional anticancer therapies. No CSC therapy has been approved by the US Food and Drug Administration. Because CSCs and normal stem cells share many characteristics, CSC-directed therapies have potential detrimental effects on normal stem cells, tissue maintenance, and development. Designing treatments that specifically target neural CSCs while allowing neural tissue stem cells to normally develop the brain is a major challenge in pediatric neuro-oncology. In recent years, better identification and characterization of neural CSCs, together with identifying differences between CSCs and normal neural stem cells, have been key factors in developing tailored therapeutics for these devastating diseases. This review focuses on the promises and challenges of pediatric neural CSC-directed therapies. We delineate the options currently in use to exhaust the ability of neural CSCs to self-renew. Finally, we suggest a comprehensive approach to combine anti-CSC therapies with other therapeutic approaches to prevent tumor recurrence.

Promises and challenges of exhausting pediatric neural cancer stem cells