Targeted drug delivery via folate receptors in recurrent ovarian cancer: a review

Abstract

Claudia Marchetti, Innocenza Palaia, Margherita Giorgini, Caterina De Medici, Roberta Iadarola, Laura Vertechy, Lavinia Domenici, Violante Di Donato, Federica Tomao, Ludovico Muzii, Pierluigi Benedetti Panici Department of Gynecology, Obstetrics and Urological Sciences, Sapienza University of Rome, Rome, Italy Abstract: Ovarian cancer is the most common cause of gynecological cancer-related mortality, with the majority of women presenting with advanced disease; although chemotherapeutic advances have improved progression-free survival, conventional treatments offer limited results in terms of long-term responses and survival. Research has recently focused on targeted therapies, which represent a new, promising therapeutic approach, aimed to maximize tumor kill and minimize toxicity. Besides antiangiogenetic agents and poly (ADP-ribose) polymerase inhibitors, the folate, with its membrane-bound receptor, is currently one of the most investigated alternatives. In particular, folate receptor (FR) has been shown to be frequently overexpressed on the surface of almost all epithelial ovarian cancers, making this receptor an excellent tumor-associated antigen. There are two basic strategies to targeting FRs with therapeutic intent: the first is based on anti-FR antibody (ie, farletuzumab) and the second is based on folate–chemotherapy conjugates (ie, vintafolide/etarfolatide). Both strategies have been investigated in Phase III clinical trials. The aim of this review is to analyze the research regarding the activity of these promising anti-FR agents in patients affected by ovarian cancer, including anti-FR antibodies and folate–chemotherapy conjugates. Keywords: ovarian cancer, targeted therapies, folate receptor, antifolate, farletuzumab, vintafolide