title: CD44: a validated target for improved delivery of cancer therapeutics.
abstract: BACKGROUND
  Advances in cancer therapeutics, namely more effective and less toxic treatments, will occur with targeting strategies that enhance the tumor biodistribution and thwart normal tissue exposure of the drug. This review focuses on cancer drug targeting approaches that exploit the expression of the cell-surface proteoglycan family, CD44, on the tumor cell surface followed by some form of ligand binding and induced CD44 internalization and intracellular drug release: in effect using this as a 'Trojan Horse' to more selectively access tumor cells.
  
  
  METHODS
  This review defines the origins of evidence for a linkage between CD44 expression and malignancy, and invokes contemporary views of the importance of putative CD44(+) cancer stem cells in disease resistance. Although the primary emphasis is on the most advanced and developed paths, those that have either made it to the clinic or are well-poised to get there, a wide scope of additional approaches at various preclinical stages is also briefly reviewed.
  
  
  CONCLUSIONS
  The future should see development of drug targeting approaches that exploit CD44 expression on CSCs/TICs, including applications to cytotoxic agents currently in the clinic.
authors.affiliation: The University of Texas, Institute of Molecular Medicine, Health Science Center, Center for Molecular Imaging, 1825 Pressler Street, SRB 330C, Houston, TX 77030, USA.
authors.forename: Sukhen C
authors.initials: SC
authors.lastname: Ghosh
authors.forename: Sultan
authors.initials: S
authors.lastname: Neslihan Alpay
authors.forename: Jim
authors.initials: J
authors.lastname: Klostergaard
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D004337:Drug Carriers / Q000008:administration & dosage; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid