Table 1.
Preclinical studies targeting the EWS-FLI1 pathway.
| Drug | Drug type | Molecular target | Mechanism | References |
|---|---|---|---|---|
| EC-8042 and EC-8105 | Chemicals (natural product, mithramycin analogs) | EWS-FLI1 protein | Represses EWS-FLI1 activity by decreasing expression of EWS-FLI1 downstream targets | (52) |
| Englerin A | Chemicals (natural product) | EWS-FLI1 protein | Inhibits cellular proliferation through a decrease in EWS-FLI1 phosphorylation and reduction its DNA binding ability | (53) |
| ESAP1 (TMRGKKKRTRAN) | Chemicals (synthetic peptide) | EWS-FLI1 protein | Impairs the transcriptional activity of EWS-FLI1 and blocks cell cycle progression | (54) |
| Romidepsin, Depsipeptide, FK228, entinostat (MS-27-275) | Chemicals (natural product, synthetic peptide) | Histone deacetylase | Reverses EWS-FLI1 mediated histone deacetylation, decreases EWS-FLI1 mRNA and protein levels, inhibits cell proliferation, and induces TRAIL-dependent apoptosis of ES cells | (55–57) |
| LSD1 inhibitor HCI-2509 | Chemicals (benzoic hydrazide) | Lysine specific demethylase 1 (Histone demethylase) | Comprehensively reverses the transcriptional profiles driven by both EWS-FLI and EWS-ERG, and markedly delays tumorigenesis in vivo | (58) |
| JIB-04 | Chemicals (pyridine hydrazone) | Jumonji domain containing histone demethylases | Deregulates oncogenic programs and increases DNA damage, resulting in impaired cell proliferation and survival, and reduced tumor growth | (59) |
| Arsenic trioxide | Chemicals (inorganic arsenic compound) | Glioma-Associated Oncogene Homolog 1 (GLI1) | Inhibits ES tumor growth via the inhibition of GLI1 | (60) |
| Methylseleninic acid (MSA) | Chemicals (organic selenium compounds) | FOXO1, Forkhead box family protein | Increases FOXO1 expression in the presence of EWS-FLI1, induces massive cell death and decreases xenograft tumor growth dependent on FOXO1 | (61, 62) |