The cerebral folate receptor alpha (FRα) transports 5-methyltetrahydrofolate (5-MTHF) into the brain.
FRα is found in many cancer types, including ovarian cancer, non-small-cell lung cancer (NSCLC), and colon cancer MDPI.
It is important in ovarian cancer treatment, where ovarian cancers frequently overexpress Folate Receptor alpha (FRα).
Low 5-MTHF in the brain causes cerebral folate deficiency (CFD).
CFD has been associated with autism spectrum disorders.
The receptor is being used as a target for new cancer treatments, including antibody-drug conjugates and other targeted therapies.
Folate receptor alpha (FRα) is a glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein encoded by the FOLR1 gene.
FRα mediates high-affinity cellular uptake of folate, which is essential for DNA synthesis, repair, and methylation, as well as for cell proliferation and survival.
FRα is expressed at low levels in most normal adult tissues.
It has physiological expression in the choroid plexus, kidney, and placenta, but is highly overexpressed in several epithelial malignancies, particularly high-grade serous ovarian carcinoma, as well as subsets of non-small cell lung, breast, and endometrial cancers.
In oncology, FRα overexpression is exploited for targeted therapy and diagnostics.
The VENTANA FOLR1 (FOLR1-2.1) RxDx Assay is an FDA-approved companion diagnostic for selecting patients with ovarian cancer eligible for mirvetuximab soravtansine.
Mirvetuximab soravtansine is an FRα-targeted antibody-drug conjugate.
Clinical trials have demonstrated significant benefit in platinum-resistant ovarian cancer patients with high FRα expression (≥75% of tumor cells with moderate to strong membrane staining).
FRα is critical for folate transport into the central nervous system.
Pathogenic variants in FOLR1 cause cerebral folate transport deficiency, leading to neurological impairment due to inadequate folate delivery across the choroid plexus into the cerebrospinal fluid.
Loss of FRα function impairs folate transport, resulting in cerebral folate deficiency and associated neurodevelopmental disorders.
Serum FRα (sFRA) is emerging as a biomarker for ovarian cancer diagnosis, prognosis, and prediction of tumor FRα expression, with higher accuracy than CA125 in some studies.