Mirvetuximab Soravtansine Emerges as Clinical Benchmark for FRα-Targeted Ovarian Cancer Therapy

Despite high initial response rates to platinum-taxane chemotherapy, epithelial ovarian cancer (EOC) remains a therapeutically challenging malignancy due to frequent recurrence and reduced platinum sensitivity. Folate receptor-alpha (FRα/FOLR1) has emerged as a key precision-oncology target, highly enriched in high-grade serous ovarian carcinoma. Its selective expression and receptor-mediated internalization make it an attractive pathway for targeted drug delivery, addressing the need for more durable and effective treatments.

This comprehensive review critically evaluated Folate receptor-alpha (FRα/FOLR1) as a multifaceted target in epithelial ovarian cancer (EOC). Researchers analyzed its role not just as a folate transporter, but also as a biomarker, drug delivery portal, immune target, and resistance-associated therapeutic axis. The manuscript expanded quantitative clinical discussions on various strategies, including PARP inhibitors, anti-angiogenic therapies, immune-checkpoint blockade, and FRα-directed antibody-drug conjugates, integrating factors like antigen density and ocular toxicity.

The review established mirvetuximab soravtansine as the current clinical benchmark, demonstrating superiority over chemotherapy in FRα-positive platinum-resistant ovarian cancer. Earlier approaches, including naked antibodies, folate-drug conjugates, peptide vaccines, and first-generation CAR-T cells, showed biological feasibility but lacked consistently durable survival benefits. The analysis highlighted critical factors influencing efficacy, such as antigen density, epithelial polarity, endocytosis/recycling, and bystander payload release. The review also discussed challenges like ocular toxicity, P-glycoprotein efflux, and tubulin-payload resistance.

The review underscored that FRα is not merely a folate transporter but a crucial biomarker, delivery portal, immune target, and resistance-associated therapeutic axis in EOC. Emerging strategies, such as eribulin-based ADCs, IgE antibodies, FRα-targeted photodynamic therapy, PET/SPECT imaging, and radioligands, are discussed as mechanism-led extensions to current therapies, aiming to overcome existing limitations.