Table 2.

Summary of selected drugs and small molecules and their effects on EWS::FLI1 and its gene signatures.

Treatment	Drug target or function	Effect on EWS::FLI1 expression	Effect on EWS::FLI1 targets
Mithramycin (143)	Binds GC rich regions	Does not alter expression	Disrupts signature, reduces activated targets
ARA-C (144)	Nucleoside analog	Reduces EWS::FLI1 protein expression	Disrupts signature, partly mimics EWS::FLI1 knockdown
Doxorubicin (144)	Standard of care chemotherapy, topoisomerase II poison	Reduces EWS::FLI1 protein expression	Disrupts signature, partly mimics EWS::FLI1 knockdown
Trabectidin (148)	DNA binding, transcriptional interference	Does not alter expression	Disrupts signature
YK-4-279 (147, 171)	Interrupts RNA helicase A binding	Does not alter expression	Disrupts signature
Rapamycin (146)	mTOR inhibitor	Reduces EWS::FLI1 expression	Disrupts signature
HDACi (multiple drugs) (37, 58, 155, 156)	HDAC inhibitors	Yes or no, depending on drug and dose	Can disrupt or reverse signature
JQ1 (73, 151)	Bromodomain inhibitor	Reduces EWS::FLI1 expression	Can disrupt or reverse signature, partly mimics EWS::FLI1 knockdown
HCI2509 (49, 72)	LSD1 inhibitor	NR	Can disrupt or reverse signature, partly mimics EWS::FLI1 knockdown
JIB-04	Histone demethylase inhibitor	Increases EWS::FLI1 expression	Can disrupt or reverse signature, partly mimics EWS::FLI1 knockdown