title: Epithelial cell adhesion molecule-targeted drug delivery for cancer therapy.
abstract: BACKGROUND
  The epithelial cell adhesion molecule (EpCAM) is abundantly expressed in epithelial tumors, on cancer stem cells and circulating tumor cells. Together with its role in oncogenic signaling, this has sparked interest in its potential for tumor targeting with antibodies and drug conjugates for safe and effective cancer therapy. Recent advances in protein engineering, linker design and drug formulations have provided a multitude of EpCAM-targeting anticancer agents, several of them with good perspectives for clinical development.
  
  
  METHODS
  This article reviews the biological, therapeutic and technical aspects of EpCAM-targeted drug delivery for cancer therapy. The authors discuss seminal findings, which distinguish EpCAM as a target with oncogenic function and abundant expression in epithelial tumors. Moreover, recent trends in engineering improved anti-EpCAM antibodies, binding proteins that are not derived from immunoglobulins and drug conjugates derived from them are highlighted and their therapeutic potential based on reported preclinical and clinical data, originality of design and perspectives are critically assessed.
  
  
  CONCLUSIONS
  EpCAM has shown promise for safe and efficient targeting of solid tumors using antibodies, alternative binding molecules and novel drug conjugates. Among the myriad of EpCAM-targeting drug delivery systems investigated so far, several could demonstrate therapeutic benefit, other formulations engineered to become tailor-made missiles are on the brink.
authors: University of Bern, Institute of Pharmacology, Friedbühlstrasse 49, CH-3010 Bern, Switzerland.
authors: Manuel
authors: M
authors: Simon
authors: Nikolas
authors: N
authors: Stefan
authors: Andreas
authors: A
authors: Plückthun
authors: Uwe
authors: U
authors: Zangemeister-Wittke
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D015815:Cell Adhesion Molecules / Q000276:immunology; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009360:Neoplastic Cells, Circulating / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D000922:Immunotoxins