KIT and PDGFRA

KIT and PDGFRA are closely related type III receptor tyrosine kinases that regulate essential cellular processes following stimulation by their respective ligands—stem cell factor for KIT and various PDGF isoforms for PDGFRA. Both have extracellular immunoglobulin-like domains, a single transmembrane helix, and a split intracellular tyrosine kinase domain. Ligand binding induces dimerization and autophosphorylation, activating downstream pathways such as PI3K/AKT, RAS/MAPK, and JAK/STAT, which together control cell growth, survival, apoptosis, and differentiation. Oncogenic mutations in KIT or PDGFRA drive the pathogenesis of gastrointestinal stromal tumors and related malignancies, making them prime targets of small molecule tyrosine kinase inhibitors including imatinib, sunitinib, regorafenib, and avapritinib. Secondary resistance due to additional mutations is a key therapeutic challenge

Other names

c-KITCD117stem cell factor receptorCD140aPDGFR-α

Inhibition of tyrosine kinase activity, blocking ATP binding to the kinase domain and therefore preventing downstream signaling required for tumor cell proliferation and survival