Factors Affecting EWS-FLI1 Activity in Ewing's Sarcoma

Table 2

Therapeutic agents targeting partners essential for EWS-FLI1.

Name	Characteristics	Effects	Reference
Mevalonate, tunicamycin	Inhibitors of N-linked glycosylation	EWS-FLI1 expression, growth arrest, inactivation of IGF-1R signaling	[12–14]
Lovastatin	HMG-CoA reductase inhibitor	Triggering of differentiation, induction of apoptosis, inactivation of IGF-1R signaling	[14, 52]
YK-4-279	Blocking RNA helicase A binding to; EWS-FLI1	Induction of apoptosis in vitro and reduction of growth in vivo	[53]
Anti-IGF-1R antibodies	Blocking IGF-1/IGF-1R pathway	Tumor growth reduction in vitro and in vivo, angiogenesis blockage, cell death induction and chemosensitivity increase	[45, 54–60]
Epigallocatechin gallate	IGF-1R inhibitor, catechin derivative	Blocks proliferation and induces cell death	[61]
Neutralizing antibody against bFGF	Blocking bFGF pathway	EWS-FLI1 downregulation through inhibition of FGFR phosphorylation	[46]
Mithramycin	DNA binding transcriptional inhibitor	EWS-FLI1 inhibitor, decreases tumor growth in vitro and in vivo	[62]
2-methoxyestradiol, bortezomib	Inhibitors of hypoxia and/or HIF-1 pathway	Induction of apoptosis, autophagy and cell cycle arrest in vitro	[63–65]
Nutlin-3a	Small molecule which antagonizes the interaction of MDM2 with p53	Stabilization of p53, apoptotic arrest, synergistic effect with other chemotherapeutic agents	[66, 67]
Ecteinascidin 743	Binds and alkylates DNA at the N2 position; of guanine	Induction of apoptosis, reduction of the activity of EWS-FLI1 targets	[68]
ARA-C (cytosine arabinoside)	Antimetabolite, inhibitor of EWS-FLI1	EWS-FLI1 protein reduction, decrease of cell viability, transformation and tumor growth in vivo	[69, 70]
Synthetic Let-7a	Synthetic miRNA	Restored Let-7a expression resulted in ESFT growth inhibition in vivo	[51]