Pair Name	Cordycepin, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Down-regulation	Expression	MMP2	hsa4313
	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Phosphorylation	MTOR	hsa2475
	Up-regulation	Cleavage	PARP1	hsa142
	Up-regulation	Phosphorylation	PRKAA1	hsa5562
	Down-regulation	Phosphorylation	RPS6KB1	hsa6198
In Vitro Model	U2OS	Osteosarcoma	Homo sapiens (Human)	CVCL_0042
	143B	Osteosarcoma	Homo sapiens (Human)	CVCL_2270
In Vivo Model	1×10⁶ suspended 143B cells in 20 µL were injected into the proximal tibia through the anterior tuberosity.
Result	This study provides comprehensive evidence that cordycepin inhibits osteosarcoma cell growth and invasion and induces osteosarcoma cell apoptosis by activating AMPK and inhibiting the AKT/mTOR signaling pathway and enhances the sensitivity of osteosarcoma cells to cisplatin, suggesting that cordycepin is a promising treatment for osteosarcoma.

Pair Name	Cordycepin, Apatinib
Partner Name	Apatinib
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Phosphorylation	PIK3CA	hsa5290
	Down-regulation	Expression	VEGFA	hsa7422
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
	PC-9	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_B260
Result	Our findings demonstrated that the combination of cordycepin and apatinib has synergistically anticancer effect on NSCLC cells by down-regulating VEGF/PI3K/Akt signaling pathway. This result indicated that cordycepin and apatinib could be a promising drug combination against NSCLC.

Pair Name	Cordycepin, Anti-CTLA-4 antibody
Partner Name	Anti-CTLA-4 antibody
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Biological Phenomena	Induction-->Immunomodulatory
In Vitro Model	MC-38	Mouse colon adenocarcinoma	Mus musculus (Mouse)	CVCL_B288
	CT26	Mouse colon adenocarcinoma	Mus musculus (Mouse)	CVCL_7254
In Vivo Model	1×10⁶ MC38 cells in 100 µL of PBS and injected them subcutaneously (s.c.) into the right flank of C57BL/6J mice. In a similar manner, we injected 1×10⁶ CT26 cells, also suspended in 100 µL of PBS, s.c. into the right flank of Balb/c mice.
Result	Our current study successfully established a combination therapeutic strategy utilizing cordycepin and CTLA-4 blockade. This strategy demonstrated a significant synergistic effect against cancer, highlighting its importance in cancer treatment.

Pair Name	Cordycepin, Temozolomide
Partner Name	Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme		Investigative
Biological Phenomena	Inhibition-->Cell metastasis
Gene Regulation	Up-regulation	Expression	CDH1	hsa999
	Down-regulation	Expression	CDH2	hsa1000
	Down-regulation	Expression	CTNNB1	hsa1499
	Down-regulation	Expression	MCL1	hsa4170
	Down-regulation	Expression	MMP9	hsa4318
	Down-regulation	Expression	MYC	hsa4609
	Down-regulation	Expression	NFKB1	hsa4790
	Up-regulation	Expression	PDCD4	hsa27250
	Down-regulation	Expression	TWIST1	hsa7291
	Down-regulation	Expression	ZEB1	hsa6935
In Vitro Model	LN-229	Glioblastoma	Homo sapiens (Human)	CVCL_0393
Result	Cordycepin combined with temozolomide may down-regulate MYC through "MicroRNA in cancer, Proteoglycans in cancer, Pathways in cancer and PI3K-AKT signaling pathway", which in turn regulate the expression of MCL1, CTNNB1, MMP9, PDCD4, thus regulating cell proliferation, migration and apoptosis in glioblastoma.

Pair Name	Cordycepin, Anti-TIGIT antibody
Partner Name	Anti-TIGIT antibody
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Biological Phenomena	Reshaped-->Tumor immune microenvironment
Gene Regulation	Up-regulation	Expression	CD226	KEGG ID N.A.
In Vitro Model	MC-38	Mouse colon adenocarcinoma	Mus musculus (Mouse)	CVCL_B288
	CT26	Mouse colon adenocarcinoma	Mus musculus (Mouse)	CVCL_7254
In Vivo Model	1×10⁶ MC38 and CT26 cells were injected into the right abdomen of C57BL/6J and Balb/c mice.
Result	The combination therapy group increased DCs in the tumor immune microenvironment and promoted cellular interaction with CD4 T cell and CD8 T cell populations while decreasing Treg cell interactions. In conclusion, cordycepin with anti-TIGIT therapy in colon cancer could reshape the tumor immune microenvironment and have notable anticancer effects.

Pair Name	Cordycepin, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	BAX	hsa581
	Down-regulation	Expression	BCL2	hsa596
	Up-regulation	Cleavage	CASP3	hsa836
	Down-regulation	Expression	CCND1	hsa595
	Down-regulation	Phosphorylation	MTOR	hsa2475
	Up-regulation	Phosphorylation	PRKAA1	hsa5562
	Up-regulation	Expression	PSMD9	hsa5715
	Down-regulation	Phosphorylation	RPS6	hsa6194
	Down-regulation	Phosphorylation	RPS6KB1	hsa6198
	Up-regulation	Phosphorylation	TP53	hsa7157
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
In Vivo Model	A total of 2×10⁶ A549 or A549DDP cells were suspended in 100 μl of normal saline and subcutaneously injected into unilateral axillary fossae of BALB/c nude mice (4 weeks old, n = 5 per group).
Result	Our results suggested that Cor in combination with DDP could be an additional therapeutic option for the treatment of DDP-resistant NSCLC.