Folate receptor alpha as a tumor target in epithelial ovarian cancer

Abstract

Objectives-Folate receptor α (FRα) is a folate-binding protein overexpressed on ovarian and several other epithelial malignancies that can be used as a target for imaging and therapeutic strategies. The goal of this study is to improve historical data that lack specific information about FRα expression in rare histological subtypes, primary disease versus metastatic foci, and recurrent disease.Methods-FRα expression was analyzed by immunohistochemistry on 186 primary and 27 recurrent ovarian tumors, including 24 pairs of samples obtained from the same individuals at diagnosis and at secondary debulking surgery. For 20 of the 186 primaries, simultaneous metastatic foci were also analyzed. FRα staining was analyzed in light of disease morphology, stage, grade, debulking status, and time from diagnosis to recurrence and death.Results-FRα expression was apparent in 134 of 186 (72%) primary and 22 of 27 (81.5%) recurrent ovarian tumors. In 21 of 24 (87.5%) matched specimens, recurrent tumors reflected the FRα status detected at diagnosis. Metastatic foci were similar to primary tumors in FRα staining. FRα status was not associated with time to recurrence or overall survival in either univariate or multivariable analyses.Conclusion-FRα expression occurs frequently, especially in the common high-grade, high-stage serous tumors that are most likely to recur. New findings from this study show that FRα expression is maintained on metastatic foci and recurrent tumors, suggesting that novel folate-targeted therapies may hold promise for the majority of women with either newly diagnosed or recurrent ovarian cancer.

IMGN853, a Folate Receptor-α (FRα)–Targeting Antibody–Drug Conjugate, Exhibits Potent Targeted Antitumor Activity against FRα-Expressing Tumors

“…High levels of FRa have been found in serous and endometrioid epithelial ovarian cancer, endometrial adenocarcinoma, and non-small cell lung cancer of the adenocarcinoma subtype (3)(4)(5)(6)(7)(8). Importantly, FRa expression is maintained in metastatic foci and recurrent carcinomas in ovarian cancer patients (9), and after chemotherapy in epithelial ovarian and endometrial cancers (10). These properties, together with the highly restricted expression of FRa on normal tissues, make FRa a highly promising target for cancer therapy, and have prompted a variety of experimental approaches for developing FRa-targeted therapies (11)(12)(13).…”

Expression of inhibitory receptors on intratumoral T cells modulates the activity of a T cell-bispecific antibody targeting folate receptor

“…20 it is overexpressed on the surface of cancer cells in a spectrum of epithelial malignancies, including ovarian, lung, renal and other solid cancers. 21,22 This tumor cell-selective expression pattern makes FolR1 an attractive candidate for targeted therapy.…”

Targeted gadolinium-loaded dendrimer nanoparticles for tumor-specific magnetic resonance contrast enhancement

“…The targeted folatedendrimer nanoparticles were taken up heavily in the liver, bowel and kidney due to excretion of the conjugates and the presence of folate receptors in these tissues. The possible clinical targets for the imaging technique presented here could be ovarian, breast, and head and neck tumors (Kalli et al 2008). Dendrimer-based delivery of contrast has several additional advantages including small size (~30 kD) comparable to size of proteins, that allows escape from vasculature and target tumor cells while also being below the threshold of renal fi ltration and therefore removing a requirement for hepatic metabolism.…”