Folate receptor alpha and CD44 antigen (FR-alpha/CD44)

The term "cells overexpressing folate and hyaluronic acid receptors" describes a specific cellular phenotype, primarily found in malignant tumors, characterized by the simultaneous upregulation of Folate Receptor Alpha (FOLR1) and the CD44 antigen. Folate receptor alpha is a glycosylphosphatidylinositol (GPI)-anchored glycoprotein that mediates the high-affinity uptake of folates required for DNA synthesis (UniProt: P15328). CD44 is a multifunctional transmembrane glycoprotein that serves as the primary receptor for hyaluronic acid, playing a critical role in cell adhesion, migration, and the maintenance of cancer stem cell properties (UniProt: P16070). In oncology, this dual-receptor profile is exploited to enhance the precision of drug delivery; therapeutic agents such as nanoparticles or antibody-drug conjugates are engineered to recognize both receptors, thereby increasing binding avidity and internalization while reducing off-target effects in healthy tissues (PubMed: 31433456). This targeting strategy is particularly relevant for aggressive cancers like ovarian, breast, and non-small cell lung carcinomas, where both receptors are frequently co-expressed and associated with poor prognosis (PubMed: 25637760).

Other names

FR-alpha and CD44 co-expressing cellsFolate receptor 1 and HCAMFOLR1 and CD44Folate and Hyaluronan receptor-positive cells

Dual-targeting ligands (folic acid and hyaluronic acid) bind to their respective receptors on the cell surface, triggering receptor-mediated endocytosis to deliver cytotoxic payloads specifically to overexpressing cells (PubMed: 28837775).