Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting

Figure 5 Cancer stem cell involvement in neuroblastoma relapse and progression, and potential therapeutic strategies. Neuroblastomas (NB) progression (center); mechanisms, molecular protagonists and conventional therapeutic strategies that select and induce the NB polyploid giant cancer cells (PGCC) and cancer stem cells (CSC), responsible for post-therapeutic relapse and low 5-year overall survival rates, in high risk unfavourable NB (right); potential therapeutic strategies to detect, target and eliminate NB PGCC and CSC subpopulations (left), and areas requiring further development (bottom). EFS: Event free survival; OS: Overall survival; CSC: Cancer stem cell; IL-2: Interleukin 2; GMCSF: Granulocyte Macrophage Colony-Stimulating Factor; NCSC: Neural crest stem cells; NB: Neuroblastomas; NK: Natural killer cells; ALK: Anaplastic lymphoma kinase; siRNA: Small interfering ribonucleic acid; PNA: Peptide nucleic acid; MSC: Mesenchymal stem cells; PGCCs: Polyploid giant cancer cells.