title: Targeting the folate receptor: diagnostic and therapeutic approaches to personalize cancer treatments.
abstract: BACKGROUND
  In cancer therapy, molecularly targeted agents have the potential to maximize antitumor efficacy while minimizing treatment-related toxicity. However, these agents may only be effective in specific tumor subtypes with defined genomic profiles. This emphasizes the importance of developing personalized cancer therapeutic strategies (i.e. through the use of companion diagnostic tests) to appropriately select and treat patients who are likely to benefit from specific targeted therapies, thus leading to improvements in clinical and safety outcomes. A potential biological target is the folate receptor (FR), which has been shown to be overexpressed on the surface of many cancers, including tumors of the lungs and ovaries.
  
  
  METHODS
  We carried out a literature search to identify how the FR can be a potential target for selected tumors, and how the FR expression can be exploited by targeted therapies.
  
  
  RESULTS
  The two main therapeutic strategies for targeting the FR are based on the use of: (i) an anti-FR antibody (e.g. farletuzumab) and (ii) folate conjugates of folate-targeted chemotherapies and companion radiodiagnostic imaging agents (e.g. vintafolide and (99m)technetium-etarfolatide). Both of these strategies are being assessed in phase III trials.
  
  
  CONCLUSIONS
  The important role that the FR plays in cancer development and progression has led to the development of FR-targeted therapeutic approaches. To date, the promising data observed in phase II clinical trials have not been confirmed in phase III studies. Accordingly, there is a need for further research in the refinement of patient selection and identification of new therapeutic combinations. In particular, the development of these targeted therapies requires reliable methods to be developed to detect FR-positive tumors in order to help select patients who may benefit from treatment.
authors.affiliation: Department of Medical Oncology, UCL Cancer Institute, London, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Ledermann
authors.affiliation: Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy silvana.canevari@istitutotumori.mi.it.
authors.forename: S
authors.initials: S
authors.lastname: Canevari
authors.affiliation: Hematology and Oncology, University of Mississippi Medical School, Jackson, USA.
authors.forename: T
authors.initials: T
authors.lastname: Thigpen
mesh_terms: D002986:Clinical Trials as Topic; D058975:Folate Receptor 1 / Q000037:antagonists & inhibitors*; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000175:diagnosis* / Q000188:drug therapy*; D057285:Precision Medicine; D011379:Prognosis
chemical_list: D058975:Folate Receptor 1; D005493:Folic Acid Antagonists
keywords: etarfolatide; folate receptor; nonsmall-cell lung cancer; ovarian cancer; vintafolide