Review Article
Overcoming Therapeutic Resistance of Bone Sarcomas: Overview of the Molecular Mechanisms and Therapeutic Targets for Bone Sarcoma Stem Cells
Table 3
Preclinical trials of novel agents targeting bone sarcoma stem cells.
| Subtype | Agents | Function | Target CSC | Mechanism | Reference |
| Osteosarcoma | LY294002 | PIK3 inhibitor | Sarcosphere | Increase the number of cells in / phase and induction of apoptosis via activation of caspase-3, caspase-9, and PARP | [87] | BRM270 | NF-κB inhibitor | CD133 | Induce IL-6 mediated apoptosis in osteosarcoma CD13 cells via downregulation of chromatin SMC2 | [91] | MC1742 | HDAC inhibitor | Sarcosphere | Inhibit sphere growth of osteosarcoma and Ewing sarcoma by apoptosis induction with increased acetyl-H3 and acetyl-tubulin levels | [95] | LNA-133a | miR-133a inhibitor | CD133 | Inhibit invasion and metastasis of osteosarcoma CD13 cells via several target genes including ANXA2 | [77] | Salinomycin | Antibacterial agent | Sarcosphere | Impair Wnt/β-catenin signaling by degradation of β-catenin | [99] | Ap-SAL-NP | Nanoparticle | CD133 | Selectively kill CD13 cells by salinomycin-loaded PEGylated polynanoparticles conjugated with CD133 aptamer | [89] | Bufalin | Unknown | Sarcosphere | Induce shrinkage of tumor spheres via activation of caspase-3 and downregulate stem cell markers, targeting miR-148 | [100] |
| Ewing sarcoma | YK-4-209 | EWS-FLI1 inhibitor | ALDH | Block RNA helicase A (RHA) binding to EWS-FLI1 | [46] | Enoxacin | Antibacterial agent | CD133 | Augment TARBP2 expression, which is repressed in CD13 Ewing cells, and reduce CD13 subpopulation through restoration of miRNA expression | [81] | miR-143,145 | Synthetic miRNA | CD133 | Repress the expression of target genes Oct3/4, Sox2, as well as EWS-FLI1 | [81] |
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