Pair Name	Costunolide, Osimertinib
Disease Info	[ICD-11: 2C25.Z]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	MAP2K1	KEGG ID N.A.
	Down-regulation	Phosphorylation	MAPK1	hsa5594
	Down-regulation	Phosphorylation	RPS6KA3	KEGG ID N.A.
	Down-regulation	Phosphorylation	AKT1	hsa207
	Down-regulation	Phosphorylation	GSK3B	hsa2932
	Down-regulation	Phosphorylation	NFKB1	hsa4790
In Vitro Model	PC-9	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_B260
	HCC827	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_2063
	NCI-H1975	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_1511
In Vivo Model	6–7 weeks old female mice with severe combined immunodeficiency (SCID) were employed to eatablish osimertinib-resistant PDX model.
Result	The combination of osimertinib and costunolide showed synergistic or additive inhibitory effects on tumor growth in osimertinib-resistant cell lines and PDX model. Hence, this study highlights a potential therapeutic strategy for osimertinib-resistant patients through targeting of MEK1 and AKT1/2 by costunolide.