Folate Receptor Alpha-A Secret Weapon in Ovarian Cancer Treatment?

Int J Mol Sci. 2024 Nov 6;25(22):11927. doi: 10.3390/ijms252211927.

Abstract

Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy worldwide. Due to its nonspecific symptoms and unreliable screening tools, EOC is not diagnosed at an early stage in most cases. Unfortunately, despite achieving initial remission after debulking surgery and platinum-based chemotherapy, most patients experience the recurrence of the disease. The limited therapy approaches have encouraged scientists to search for new detection and therapeutic strategies. In this review, we discuss the role of folate receptor alpha (FRα) in EOC development and its potential application as a biomarker and molecular target in designing new EOC screening and treatment methods. We summarize the mechanisms of the action of various therapeutic strategies based on FRα, including MABs (monoclonal antibodies), ADCs (antibody-drug conjugates), FDCs (folate-drug conjugates), SMDCs (small molecule-drug conjugates), vaccines, and CAR-T (chimeric antigen receptor T) cells, and present the most significant clinical trials of some FRα-based drugs. Furthermore, we discuss the pros and cons of different FR-based therapies, highlighting mirvetuximab soravtansine (MIRV) as the currently most promising EOC-targeting drug.

Keywords: MIRV; antibody–drug conjugates; biomarker; chimeric antigen receptor T; epithelial ovarian cancer; folate–drug conjugates; monoclonal antibodies; small molecule–drug conjugates; vaccines; vintafolide.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Ovarian Epithelial / drug therapy
  • Carcinoma, Ovarian Epithelial / metabolism
  • Carcinoma, Ovarian Epithelial / therapy
  • Female
  • Folate Receptor 1* / antagonists & inhibitors
  • Folate Receptor 1* / metabolism
  • Humans
  • Immunoconjugates / therapeutic use
  • Maytansine / analogs & derivatives
  • Molecular Targeted Therapy / methods
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / metabolism
  • Ovarian Neoplasms* / therapy

Substances

  • Folate Receptor 1
  • mirvetuximab soravtansine
  • Biomarkers, Tumor
  • Immunoconjugates
  • FOLR1 protein, human
  • Antibodies, Monoclonal
  • Maytansine
  • Antibodies, Monoclonal, Humanized

Grants and funding

This research received no external funding.