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.