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Joyce F. Liu, MD, MPH
Joyce F. Liu, MD, MPH
Posted: Tuesday, January 21, 2025
The increased morbidity and mortality associated with epithelial ovarian cancer have motivated clinical scientists to investigate new diagnostic and therapeutic strategies, according to a study published in the International Journal of Molecular Sciences. These efforts have identified the transmembrane glycoprotein folate receptor alpha (FRα) as a potential biomarker and molecular target that may improve clinical outcomes for this patient population, emphasized Karol Bukowski, PhD, of the University of Lodz, Poland, and colleagues.
The role of folate in carcinogenesis remains under debate. However, it is speculated that folate may play a critical role in cancer cell growth through increased cell turnover. In both primary and recurrent ovarian cancers, an increased expression of FRα has been observed. Given there is a limited expression of FRα in normal tissues, the receptor serves a favorable biomarker for patients with epithelial ovarian cancer. In addition, the histologic stage and grade of the primary cancer seem to be correlated with FRα expression.
FRα as a therapeutic target provides many beneficial opportunities for drug design and clinical outcomes, according to the investigators. The receptor’s ability to absorb relatively large compounds does not limit the overall design of potential therapeutic agents. In addition, FRα is located on the apical surface and thus would reduce the risk of drug-related adverse events experienced by patients. Moreover, despite treatment with chemotherapy, FRα maintains a consistent expression in recurrent and metastatic tumors, making it a favorable therapeutic target, Dr. Bukowski and colleagues noted.
Various strategies to target FRα have been proposed, including monoclonal antibodies, antibody-drug conjugates, folate-drug conjugates, small molecule–drug conjugates, vaccines, and FRα-specific chimeric antigen receptor T-cell therapies. In November 2022, the FRα-targeting antibody-drug conjugate mirvetuximab soravtansine-gynx was approved as a treatment option for patients with FRα-positive platinum-resistant ovarian cancer. Numerous studies focused on developing novel therapies to improve clinical outcomes for this patient population are underway.
Disclosure: The study authors reported no conflicts of interest.
International Journal of Molecular Sciences
