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Role of the folate receptor in ovarian cancer treatment: evidence, mechanism, and clinical implications

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Abstract

Folate can be transported into the cell by the reduced folate carrier (RFC), the proton-coupled folate transporter (PCFT), or the folate receptor (FR), of which various isoforms exist. While the RFC and PCFT are expressed by many normal cells, the FR is present only in a small proportion of normal tissues. In these tissues, the FR expression level is often low and restricted to the apical surface of polarized epithelial cells. In contrast, FR is expressed on the blood-accessible basal and lateral membranes of many types of epithelial cancer. Considering that FR is expressed in few nonmalignant cell types on luminal membranes generally not accessible for molecules transported in the blood, FR is considered a promising antitumor target. As FR expression seems associated with tumor progression and prognosis, anticancer therapies targeting FR are currently being developed, such as farletuzumab (Morphotek, Exton, PA, USA), IMGN853 (ImmunoGen, Waltham, MA, USA), vintafolide, and EC1456 (both Endocyte Inc., West Lafayette, IN, USA). FR expression could be used as a response-predictive biomarker for these treatments. The ability to identify patients and treat them with an effective therapy based on the known expression of the tumor marker would, indeed, be the next step in predictive medicine for these patients. This review summarizes the role of FR in ovarian cancer and the value of FR as a prognostic biomarker for ovarian cancer and a response-predictive biomarker for folate-targeted therapeutics.

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Acknowledgments

Editorial and medical writing assistance was provided by Anna Hooijkaas, PhD, TRM Oncology, The Hague, The Netherlands, funded by Endocyte Inc., West Lafayette, IN, USA. The authors are fully responsible for content and editorial decisions for this manuscript.

Conflict of interest

IV received honoraria for advisory boards for Endocyte and Merck. CM received honoraria for advisory boards for Endocyte and Merck. RC served on steering committees for Merck, Endocyte, and Morphotek/Eisai and received research funding from Merck.

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  1. Department of Obstetrics and Gynaecolog, Leuven Cancer Institute, University Hospital Leuven, Herestraat 49, 3000, Leuven, Belgium

    Ignace B. Vergote

  2. Innsbruck Medical University, Anichstrasse 35, 6020, Innsbruck, Austria

    Christian Marth

  3. University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1362, Houston, TX, 77030-4009, USA

    Robert L. Coleman

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Vergote, I.B., Marth, C. & Coleman, R.L. Role of the folate receptor in ovarian cancer treatment: evidence, mechanism, and clinical implications. Cancer Metastasis Rev 34, 41–52 (2015). https://doi.org/10.1007/s10555-014-9539-8

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