title: Emerging strategies for EphA2 receptor targeting for cancer therapeutics.
abstract: BACKGROUND
  High mortality rates with cancers warrant further development of earlier diagnostics and better treatment strategies. Membrane-bound erythropoietin-producing hepatocellular receptor tyrosine kinase class A2 (EphA2) is overexpressed in breast, prostate, urinary bladder, skin, lung, ovary and brain cancers.
  
  
  METHODS
  EphA2 overexpression in cancers, its signaling mechanisms and strategies to target its deregulation.
  
  
  RESULTS
  High EphA2 expression in cancer cells is correlated with a poor prognosis associated with recurrence due to enhanced metastasis. Interaction of the EphA2 receptor with its ligand (e.g., ephrinA1) triggers events that are deregulated and implicated in carcinogenesis. EphrinA1-independent oncogenic activity and ephrinA1-dependent tumor suppressor roles for EphA2 are described. Molecular interactions of EphA2 with signaling proteins are associated with the modulation of cytoskeleton dynamics, cell adhesion, proliferation, differentiation and metastasis. The deregulated signaling by EphA2 and its involvement in oncogenesis provide multiple avenues for the rational design of intervention approaches.
  
  
  CONCLUSIONS
  EphA2 has been tested as a drug target using multiple approaches such as agonist antibodies, RNA interference, immunotherapy, virus vector-mediated gene transfer, small-molecule inhibitors and nanoparticles. With over a decade of research, encouraging results with targeting of EphA2 expression in various pre-clinical cancer models necessitate further studies.
authors.affiliation: Purdue University, Department of Comparative Pathobiology, Bindley Bioscience Center, West Lafayette, IN 47907, USA.
authors.forename: Manish
authors.initials: M
authors.lastname: Tandon
authors.forename: Sai Vikram
authors.initials: SV
authors.lastname: Vemula
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Mittal
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016503:Drug Delivery Systems; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009369:Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D011379:Prognosis; D036104:Receptor, EphA2 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D036104:Receptor, EphA2