Folate receptor and folate transport system (FR/FTS)

Folate receptors (FRs) and folate transport systems are a group of membrane proteins that facilitate the cellular uptake of folates, which are essential for one-carbon metabolism and DNA synthesis [UniProt P15328, P41440]. The system includes high-affinity receptors (FRα, FRβ, FRγ) and transporters such as the Reduced Folate Carrier (RFC) and the Proton-Coupled Folate Transporter (PCFT) [PubMed: 21685213]. Folate receptor alpha (FRα) is significantly overexpressed in various epithelial malignancies, including ovarian and non-small cell lung cancers, while maintaining low expression in normal tissues [PubMed: 32803198]. This differential expression makes FRα a primary target for antibody-drug conjugates (ADCs) like mirvetuximab soravtansine, which delivers cytotoxic agents directly to tumor cells [FDA: Elahere]. Additionally, FRβ is expressed on activated macrophages in inflammatory diseases, providing a target for imaging and therapy in conditions like rheumatoid arthritis [PubMed: 25103571]. Antifolate drugs, such as methotrexate and pemetrexed, exploit these transport systems to enter cells and inhibit enzymes required for nucleotide biosynthesis, thereby arresting cell proliferation [StatPearls: Methotrexate]. The Proton-Coupled Folate Transporter (PCFT) is crucial for intestinal folate absorption and is often involved in hereditary folate malabsorption [PubMed: 17308537]. Overall, these systems represent a versatile platform for both targeted drug delivery and metabolic inhibition in oncology and immunology.

Other names

FOLR1FOLR2FOLR3SLC19A1SLC46A1Reduced folate carrierProton-coupled folate transporterFolate receptor alphaFolate receptor betaFolate receptor gammaFolate binding protein

Receptor-mediated endocytosis of folate-drug conjugates and facilitated or active transport of antifolates into the cytoplasm to inhibit folate-dependent enzymes.