Folate receptor family (FR) (FR)

The folate receptor (FR) family consists of high-affinity glycosylphosphatidylinositol (GPI)-anchored glycoproteins that mediate the uptake of folates and folate-derivatives into cells through receptor-mediated endocytosis (Source: UniProt, P15328). The family includes four distinct isoforms: FR-alpha (FOLR1), FR-beta (FOLR2), FR-gamma (FOLR3), and FR-delta (FOLR4), which exhibit highly specific tissue distribution patterns (Source: PubMed, PMID: 32833105). FR-alpha is the most prominent therapeutic target, as it is significantly overexpressed in various solid tumors, particularly ovarian, non-small cell lung, and triple-negative breast cancers, while remaining largely absent in most healthy tissues (Source: NIH, National Cancer Institute). FR-beta is primarily expressed on myeloid cells and is a target of interest in inflammatory conditions like rheumatoid arthritis and within the tumor microenvironment (Source: PubMed, PMID: 29158374). Therapeutic strategies targeting these receptors include antibody-drug conjugates (ADCs), such as the FDA-approved mirvetuximab soravtansine, as well as small molecule drug conjugates and radio-ligand therapies (Source: FDA.gov). Beyond its role in cancer, the folate receptor family is essential for embryonic development, and its dysfunction is associated with neural tube defects and cerebral folate deficiency syndromes (Source: StatPearls).

Other names

Folate binding proteinFBPFOLRFolate receptor alphaFolate receptor betaFolate receptor gammaFolate receptor deltaAdult folate-binding proteinKB cells antigen

Drugs targeting the folate receptor family, particularly FR-alpha, primarily function by binding to the receptor on the cell surface and undergoing internalization via receptor-mediated endocytosis (Source: PubMed, PMID: 31513018). For antibody-drug conjugates (ADCs), the internalized complex is processed in lysosomes, releasing a cytotoxic payload that induces cell death. Other mechanisms include the use of monoclonal antibodies to trigger antibody-dependent cellular cytotoxicity (ADCC) or the use of folate-conjugated radiopharmaceuticals for targeted imaging and therapy (Source: Journal of Clinical Oncology).