Clinical translation of folate receptor-targeted therapeutics

Expert Opin Drug Deliv. 2012 Aug;9(8):901-8. doi: 10.1517/17425247.2012.694863. Epub 2012 Jun 5.

Abstract

Introduction: Folate receptor-α (FR-α) has been established as a membrane marker for ovarian cancer. In addition, it is frequently overexpressed in other major types of epithelial tumors. FR-α-based tumor-targeted therapy and drug carriers have been an active area of laboratory research for more than 20 years. Recently, there has been a great increase in the effort to finally translate this promising technology into the clinic and bring FR-targeted therapeutics into the market.

Areas covered: Two FR-targeted therapeutic agents have moved into Phase III clinical trials, the monoclonal antibody farletuzumab and the low molecular weight vintafolide, combined with etarfolatide as a companion imaging agent, representing two alternative strategies for targeting the FR.

Expert opinion: Each of the two strategies has advantages and disadvantages. Identification of the best target patient population is likely critical to the ultimate success of FR-targeted agents in the clinic. A successful clinical strategy may require the integration between FR expression analysis and an optimal combination of FR-targeted therapy and standard chemotherapy. Advancement into Phase III trials and the ongoing clinical development of several additional folate conjugates are likely to usher in a new era of clinical translation and validation of FR-targeted imaging and therapeutic agents.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Carrier Proteins
  • Clinical Trials as Topic
  • Diagnostic Imaging
  • Drug Delivery Systems*
  • Female
  • Folate Receptors, GPI-Anchored / antagonists & inhibitors
  • Folic Acid / administration & dosage
  • Folic Acid / analogs & derivatives*
  • Humans
  • Ovarian Neoplasms / drug therapy*
  • Receptors, Cell Surface / metabolism
  • Vinca Alkaloids / administration & dosage*

Substances

  • Antibodies, Monoclonal, Humanized
  • Carrier Proteins
  • EC145
  • Folate Receptors, GPI-Anchored
  • Receptors, Cell Surface
  • Vinca Alkaloids
  • farletuzumab
  • Folic Acid