Table 1.

Summary of EphA2 targeted therapies against cancer

Mechanism	Method or compound	Cancer type	Exact effects on EphA2	Effects in vitro	Effects in vivo	Ref.
Decrease EphA2 expression
	EPHARNA	Ovarian cancer	Decrease in vivo EphA2 expression	–	Inhibit tumor growth	[49]
Promote EphA2 degradation
	Soluble ephrin A1 and ephrin A1-Fc
	Ephrin A1	Glioblastoma multiforme	Induce EphA2 internalization and downregulation	Inhibit cell migration		[50]
	Monomeric ephrin A1	Breast cancer	Induce EphA2 phosphorylation and degradation	–	–	[51]
	Ephrin A1-Fc	Pancreatic cancer	Induce EphA2 degradation	Inhibit cell motility and invasion	–	[52]
	Ephrin A1-Fc	Gastric cancer	Induce EphA2 phosphorylation and degradation	Inhibit cell growth	–	[53]
	EphA2 monoclonal antibody
	EA1.2	Breast cancer	Induce EphA2 phosphorylation and degradation	Inhibit cell growth, disrupt angiogenesis	–	[45]
	EA2 and B233	Breast cancer	Induce EphA2 phosphorylation and degradation	inhibit tumor growth in vivo	Inhibit tumor growth	[54]
	D2 scFv	Lymphoma	Prevent EphA2-ephrin interaction	Inhibit cell proliferation, induce apoptosis	–	[55]
	SHM16	Melanoma	Antibody internalization	Inhibit cell migration and invasion	–	[43]
	DS-8895a	Breast cancer and gastric cancer	Inhibit EphA2 phosphorylation	–	Inhibit tumor growth	[56]
	DS-8895a	Breast cancer and gastric cancer	–	–	Inhibit tumor growth	[57]
	3F2-3M	Breast, ovarian, non-small cell lung cancer	Induce EphA2 phosphorylation	Kill tumor cells in vitro	Inhibit tumor growth	[44]
Block endogenous EphA2 activation
	Inhibit Eph-ephrin interactions
	EphA2-Fc	Pancreatic	Inhibit EphA2 phosphorylation	Inhibit angiogenesis	Inhibit tumor growth	[58]
	Lithocholic acid	Prostate and colon cancer	Inhibit EphA2 phosphorylation	Inhibit cell rounding, retraction	–	[59]
	UniPR126	Prostate cancer	Inhibit EphA2 phosphorylation	Inhibit cell rounding, retraction	–	[60]
	UniPR126	Prostate cancer	Inhibit EphA2 phosphorylation	–	–	[61]
	UniPR129	Prostate cancer	Inhibit EphA2 phosphorylation and block kinase domain enzymatic activity	Inhibit cell rounding, disrupt angiogenesis		[62]
	UniPR1331	Prostate cancer	block EphA2 phosphorylation and activation	Disrupt angiogenesis	–	[63]
	Cholanic acid	Prostate cancer	Inhibit EphA2 phosphorylation	Inhibit cell retraction	–	[64]
	GW4064	Prostate cancer	Inhibit EphA2 phosphorylation	–	–	[65]
	76D10	Prostate cancer	Inhibit EphA2 phosphorylation	Inhibit cell retraction	–	[66]
	Inhibit kinase activity of EphA2
	Dasatinib	Melanoma	Inhibit EphA2 phosphorylation and kinase activity	Inhibit cell migration and invasion	–	[67]
	Dasatinib	Pancreatic cancer	Inhibit EphA2 phosphorylation and kinase activity	Inhibit cell growth	–	[68]
	Candidate 4a	Glioblastoma	–	Inhibit cell survival	–	[69]
	ALW-II-41-27	Non-small cell lung cancer	Inhibit EphA2 phosphorylation	Inhibit cell survival	Inhibit tumor growth	[70]
	ALW-II-41-27	Lung cancer	–	Inhibit cell survival, proliferation, migration, increased apoptosis	Inhibit tumor growth	[25]
EphA2 as drug delivery target
	Peptide/antibody-drug conjugates
	Ephrin A1–PE38QQR	Glioblastoma multiforme	Decrease EphA2 expression	Inhibit cell survival	–	[71]
	MEDI-547	Prostate cancer	Induce EphA2 phosphorylation and degradation	Inhibit cell survival	Inhibit tumor growth	[72]
	MEDI-547	Endometrial cancer	Induce EphA2 internalization and degradation	Inhibit cell survival, induce apoptosis	Inhibit tumor growth	[73]
	MEDI-547	Ovarian cancer	Induce EphA2 degradation	Inhibit cell survival and proliferation, induce apoptosis	Inhibit tumor growth	[74]
	Antibody-directed nanotherapeutics
	YTPL	Melanoma	–	Inhibit cell survival	–	[75]
	MM-310	Breast, prostate, gastric, and esophageal cancer	–	–	Inhibit tumor growth	[76]
EphA2-based immunotherapy
	DC-vaccine	Colon cancer (murine)	–	–	Inhibit tumor growth	[77]
	DC-vaccine	Colon cancer (murine) and melanoma (human)	–	–	Inhibit tumor growth	[78]
	CAR T cells	Glioblastoma	Decrease EphA2 expression	–	Inhibit tumor growth	[79]
	CAR T cells	Glioma	–	–	Inhibit tumor growth	[80]
	CAR T cells	Lung cancer	–	Inhibit cell survival	Inhibit tumor growth	[81]
	CAR T cells	Esophageal squamous cell carcinoma	–	Inhibit cell survival	–	[82]