Targeting the folate receptor for the treatment of ovarian cancer
While conventional therapies have improved the outcome for patients with ovarian cancer, the disease still accounts for the most gynecological cancer-related deaths. The development of new treatment options is needed and efforts have focused on targeted therapies which aim to improve patient outcome by increasing anti-tumor activity while minimizing toxicity. The frequent overexpression of folate receptor α (FRα) in ovarian cancer has provided the rationale for new promising therapeutic approaches that target this surface protein. Clinical evaluations of compounds that utilize two basic approaches to FR targeting have been conducted or are ongoing. One approach is based on conjugates of folate analogs, such as vintafolide, where payloads are delivered by targeting the high affinity folate binding site of the receptor. A second approach is to use antibodies or antibody-like binders that target the FRα protein. Both naked antibodies (farletuzumab) and antibody conjugates (IMGN853) are being evaluated. This review summarizes the rationale for targeting FRα in ovarian cancer and provides an overview of the promising FRα-targeting compounds being developed.