Folate receptor and transporter (FR/FT)

The folate receptor and transporter system is a collective group of proteins responsible for the uptake and intracellular distribution of folates, which are essential B-vitamins required for one-carbon metabolism, nucleotide synthesis, and methylation reactions [1, 4]. This system primarily includes the high-affinity folate receptors (FR-alpha, FR-beta, and FR-gamma) and the solute carrier transporters, namely the reduced folate carrier (RFC/SLC19A1) and the proton-coupled folate transporter (PCFT/SLC46A1) [1, 14]. FR-alpha is of particular clinical interest as it is highly overexpressed in various epithelial cancers, such as ovarian, lung, and breast cancers, while having limited expression in normal tissues [9, 13]. This differential expression provides a therapeutic window for targeted agents like antibody-drug conjugates, such as mirvetuximab soravtansine [12, 13]. Transporters like RFC and PCFT are the primary routes for the entry of classical antifolates like methotrexate and pemetrexed into cells [15, 16]. Dysregulation or genetic mutations in these proteins are associated with conditions such as cerebral folate deficiency, hereditary folate malabsorption, and cancer progression [8, 15]. Therapeutic strategies involve both the use of antifolates that compete for transport and the development of targeted therapies that exploit receptor overexpression for selective drug delivery [1, 10].

Other names

Folate transport systemFolate uptake systemFolate binding proteinFolate receptor familyFolate transporters

Antifolates act as competitive inhibitors of folate transporters and enzymes to disrupt DNA synthesis; targeted therapies utilize high-affinity receptors for selective delivery of cytotoxic payloads or immune-mediated cell killing.