The EphA2 and cancer connection: potential for immune-based interventions.

Publication date: Sep 29, 2020

The Eph (erythropoietin-producing human hepatocellular) receptors form the largest known subfamily of receptor tyrosine kinases. These receptors interact with membrane-bound ephrin ligands via direct cell-cell interactions resulting in bi-directional activation of signal pathways. Importantly, the Eph receptors play critical roles in embryonic tissue organization and homeostasis, and in the maintenance of adult processes such as long-term potentiation, angiogenesis, and stem cell differentiation. The Eph receptors also display properties of both tumor promoters and suppressors depending on the cellular context. Characterization of EphA2 receptor in regard to EphA2 dysregulation has revealed associations with various pathological processes, especially cancer. The analysis of various tumor types generally identify EphA2 receptor as overexpressed and/or mutated, and for certain types of cancers EphA2 is linked with poor prognosis and decreased patient survival. Thus, here we highlight the role of EphA2 in malignant tissues that are specific to cancer; these include glioblastoma multiforme, prostate cancer, ovarian and uterine cancers, gastric carcinoma, melanoma, and breast cancer. Due to its large extracellular domain, therapeutic targeting of EphA2 with monoclonal antibodies (mAbs), which may function as inhibitors of ligand activation or as molecular agonists, has been an oft-attempted strategy. Therefore, we review the most current mAb-based therapies against EphA2 expressing cancers currently in pre-clinical and/or clinical stages. Finally, we discuss the latest peptides and cyclical-peptides that function as selective agonists for EphA2 receptor.

Concepts Keywords
Angiogenesis Cancers
Breast Cancer Properties tumor
Cancer Cancers EphA2
Ephrin Tyrosine kinase receptors
Erythropoietin Branches of biology
Extracellular Cell biology
Gastric Carcinoma Single-pass transmembrane proteins
Glioblastoma Multiforme Ephrin receptor
Homeostasis EPH receptor A2
Interact Receptor tyrosine kinase
Ligand Cell signaling
Ligands Antibodies
Long Term Potentiation
Malignant
Melanoma
Membrane
Monoclonal Antibodies
Peptides
Prognosis
Prostate Cancer
Receptor
Receptors
Subfamily
Tumor
Tyrosine
Uterine

Semantics

Type Source Name
disease MESH cancer
drug DRUGBANK Erythropoietin
drug DRUGBANK L-Tyrosine
pathway KEGG Long-term potentiation
disease MESH pathological processes
disease MESH glioblastoma multiforme
drug DRUGBANK Methylergometrine
disease MESH cancers gastric
disease MESH carcinoma
disease MESH melanoma
pathway KEGG Melanoma
disease MESH breast cancer
pathway KEGG Breast cancer

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