Platelet-derived growth factor receptor (PDGFR) (PDGFR)

Platelet-derived growth factor receptors (PDGFRs) are cell-surface receptor tyrosine kinases that play essential roles in regulating cell growth, proliferation, and survival [1][8]. The family consists of two main subunits, PDGFR-alpha (PDGFRA) and PDGFR-beta (PDGFRB), which form homo- or heterodimers upon binding their respective platelet-derived growth factor (PDGF) ligands [1][4]. In healthy tissues, PDGFR signaling is critical for embryonic development, wound healing, and the maintenance of connective tissue by stimulating mesenchymal cells like fibroblasts and smooth muscle cells [3][11]. Dysregulation of this pathway, often through activating mutations, gene fusions, or overexpression, is a significant driver in various malignancies, including gastrointestinal stromal tumors (GIST), dermatofibrosarcoma protuberans, and certain types of leukemia and glioma [5][6]. Pharmacological targeting of PDGFR is a well-established strategy in oncology and the management of fibrotic diseases [12]. Most therapeutic agents are small-molecule tyrosine kinase inhibitors (TKIs), such as imatinib and sunitinib, which block the intracellular kinase domain by competing with ATP [7][9]. Additionally, monoclonal antibodies like olaratumab have been developed to target the extracellular domain and prevent ligand binding [11]. Clinical use of these inhibitors often requires monitoring for specific genetic biomarkers, such as PDGFRA mutations, to predict efficacy. However, therapeutic use can be associated with safety concerns, most notably fluid retention, periorbital edema, and potential cardiovascular toxicity [6][7].

Other names

Platelet-derived growth factor receptorPDGF receptorCD140PDGFRAPDGFRBPlatelet-derived growth factor receptor family

ATP-competitive inhibition of the intracellular tyrosine kinase domain and monoclonal antibody-mediated neutralization of the extracellular ligand-binding site [1][7][11].