Therapeutic strategies targeting folate receptor α for ovarian cancer

Abstract

Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and presents a major clinical challenge due to limited treatment options. Folate receptor alpha (FRα), encoded by the FOLR1 gene, is an attractive therapeutically target due to its prevalent and high expression in EOC cells. Recent basic and translational studies have explored several modalities, such as antibody-drug conjugate (ADC), monoclonal antibodies, small molecules, and folate-drug conjugate, to exploit FRα for EOC treatment. In this review, we summarize the function of FRα, and clinical efficacies of various FRα-based therapeutics. We highlight mirvetuximab soravtansine (MIRV), or Elahere (ImmunoGen), the first FRα-targeting ADC approved by the FDA to treat platinum-resistant ovarian cancer. We discuss potential mechanisms and management of ocular adverse events associated with MIRV administration.

PROTACs in Ovarian Cancer: Current Advancements and Future Perspectives

“…Further research is needed to investigate new POIs that may provide therapeutic benefits in EOC, as well as to better characterize the activity of existing PROTACs targeting POIs in EOC using in vivo EOC models such as xenografts, PDXs, and immunocompetent syngeneic models. An exciting development in the field has been the use of a folate-caged PROTAC for targeted delivery to FRα-expressing cells, which has high relevance for EOC [25,38,39]. Future work focused on additional delivery systems, such as nanoparticles, degrader-antibody conjugates, and opto-PROTACs, will provide further opportunities to refine PROTAC delivery and selectivity for EOC.…”

“…Relevant to EOC, Liu and colleagues further modified ARV-771, creating a folate-caged version [25]. Folate receptor α (FRα) is an important target for drug delivery in EOC, given its increased expression in malignant ovarian cancer relative to benign conditions or the normal ovary, its localization on the plasma membrane, and its ability to internalize large molecules through receptor-mediated endocytosis [38,39]. Consistently, the first FRα-targeted agent was recently FDA-approved for the treatment of recurrent EOC [40].…”