title: The transferrin receptor and the targeted delivery of therapeutic agents against cancer.
abstract: BACKGROUND
  Traditional cancer therapy can be successful in destroying tumors, but can also cause dangerous side effects. Therefore, many targeted therapies are in development. The transferrin receptor (TfR) functions in cellular iron uptake through its interaction with transferrin. This receptor is an attractive molecule for the targeted therapy of cancer since it is upregulated on the surface of many cancer types and is efficiently internalized. This receptor can be targeted in two ways: 1) for the delivery of therapeutic molecules into malignant cells or 2) to block the natural function of the receptor leading directly to cancer cell death.
  
  
  METHODS
  In the present article we discuss the strategies used to target the TfR for the delivery of therapeutic agents into cancer cells. We provide a summary of the vast types of anti-cancer drugs that have been delivered into cancer cells employing a variety of receptor binding molecules including Tf, anti-TfR antibodies, or TfR-binding peptides alone or in combination with carrier molecules including nanoparticles and viruses.
  
  
  CONCLUSIONS
  Targeting the TfR has been shown to be effective in delivering many different therapeutic agents and causing cytotoxic effects in cancer cells in vitro and in vivo.
  
  
  CONCLUSIONS
  The extensive use of TfR for targeted therapy attests to the versatility of targeting this receptor for therapeutic purposes against malignant cells. More advances in this area are expected to further improve the therapeutic potential of targeting the TfR for cancer therapy leading to an increase in the number of clinical trials of molecules targeting this receptor. This article is part of a Special Issue entitled Transferrins: molecular mechanisms of iron transport and disorders.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Tracy R
authors.initials: TR
authors.lastname: Daniels
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Bernabeu
authors.forename: José A
authors.initials: JA
authors.lastname: Rodríguez
authors.forename: Shabnum
authors.initials: S
authors.lastname: Patel
authors.forename: Maggie
authors.initials: M
authors.lastname: Kozman
authors.forename: Diego A
authors.initials: DA
authors.lastname: Chiappetta
authors.forename: Eggehard
authors.initials: E
authors.lastname: Holler
authors.forename: Julia Y
authors.initials: JY
authors.lastname: Ljubimova
authors.forename: Gustavo
authors.initials: G
authors.lastname: Helguera
authors.forename: Manuel L
authors.initials: ML
authors.lastname: Penichet
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000008:administration & dosage / Q000378:metabolism; D016503:Drug Delivery Systems; D005822:Genetic Vectors; D006801:Humans; D007501:Iron / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*; D011990:Receptors, Transferrin / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D011990:Receptors, Transferrin; D007501:Iron