II. Indications

  1. Gastrointestinal Stromal Tumor (c-KIT+, adjuvant after complete tumor resection)

III. Mechanism

  1. Stem Cell Factor (SCF, tumor-associated antigen Mast Cell factor)
    1. SCF is expressed during Embryogenesis, and binds and activates C-Kit Tyrosine Kinase Receptors
    2. SCF is a growth factor for multiple cell types (esp. hematopoietic cells)
      1. Mast Cell differentiation and function
      2. Melanocytes
  2. C-Kit Cell Surface Protein (Stem Cell Factor Receptor or SCFR)
    1. C-Kit is a transmembrane Protein and receptor Tyrosine Kinase, activated on binding by Stem Cell Factor (SCF)
    2. C-Kit is an important factor in the regulation of cell differentiation and proliferation
    3. C-Kit is overexpressed in some solid and Hematologic Cancers (e.g. GI stromal tumors)
  3. C-Kit Inihibitors
    1. Inhibit specific C-Kit mutations, overexpressed in certain tumors, reducing their cell proliferation

IV. Medications: c-KIT Inhibitors

  1. See BCR-ABL Inhibitor
  2. Nilotinib (Tasigna)
    1. Binds and stabilizes inactive ABL Protein kinase, with greater potency and less resistance than Imatinib
    2. Also a Platelet-derived growth factor receptor Antagonist (PDGF-R inhibitor) and c-KIT Inhibitor
    3. Risk of Prolonged QT, myelosuppression, Hemorrhage, Pneumonia, Pancreatitis, Peripheral Arterial Disease progression
    4. Avoid with moderate-strong CYP3A Inhibitors and Inducers
    5. Take on empty Stomach (increased absorption and toxicity risk with food)
  3. Imatinib mesylate (Gleevec)
    1. BCR-ABL Inhibitor and also a Stem Cell Factor (SCF) and c-KIT Inhibitor (Tyrosine Kinase KIT Gene Inhibitor)
    2. Also a Platelet-derived growth factor inhibitor (PDGF Inhibitor)
    3. Risk of edema, Tumor Lysis Syndrome, myelosuppression, hepatotoxicity, bleeding, Stevens Johnson Syndrome, pseudoporphyria
    4. Avoid with moderate-strong CYP3A Inhibitors and Inducers
    5. Increases Warfarin levels and INR, and increases Acetaminophen levels
    6. Also approved in children for ALL (Philadelphia Chromosome positive)
    7. Decreased dosing in renal dysfunction

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Ontology: Stem Cell Factor (C0143630)

Definition (NCI_NCI-GLOSS) A substance that causes blood stem cells (cells from which other types of cells develop) to change into different types of blood cells and increases the number and actions of these cells in the blood. Kit ligand is a type of cytokine and a type of growth factor.
Definition (NCI) Stem Cell Factor is a hematopoietic growth factor, a key signal in mast cell differentiation and function, and a ligand for the KIT tyrosine kinase receptor CD117. In the mouse, this growth factor is encoded by Sl ('steel'), a gene critical to the development of several cell lineages as well as to hematopoiesis in the adult. SCF augments proliferation of myeloid and lymphoid progenitors. (from OMIM 184745 and NCI)
Definition (CSP) expressed during embryogenesis and provides key signal in multiple aspects of mast cell differentiation and function; hematopoietic growth factor and ligand of c-kit receptor CD117.
Definition (MSH) A hematopoietic growth factor and the ligand of the cell surface c-kit protein (PROTO-ONCOGENE PROTEINS C-KIT). It is expressed during embryogenesis and is a growth factor for a number of cell types including the MAST CELLS and the MELANOCYTES in addition to the HEMATOPOIETIC STEM CELLS.
Concepts Biologically Active Substance (T123) , Amino Acid, Peptide, or Protein (T116)
MSH D019089
SnomedCT 58613001
English mast cell growth factor, Mast Cell Growth Factor, Steel Factor, Stem Cell Factor, c kit Ligand, c-kit Ligand, kit Ligand, Stem Cell Factor [Chemical/Ingredient], scf, stem cell factor (SCF), Kit ligand, stem cell factor, kit ligand, MCGF, Mast cell growth factor, SCF, KITLG, Kit Ligand, MGF Stem Cell Factor, MGF, C-Kit Ligand
German Mastzellen-Wachstumsfaktor, C-Kit-Ligand, C-kit Ligand, Stammzell-Faktor, Steel-Faktor, Steel Factor, Stammzellen-Faktor, Stammzellfaktor, Mastzellenwachstumsfaktor, Stammzellenfaktor
Swedish Stemcellsfaktor
Czech faktor růstu kmenových buněk
Portuguese Fator de Células-Tronco, Fator de Crescimento do Mastócitos, Fator de Célula-Tronco, Fator de Crescimento do Mastócito, Fator de Steel, Ligante c-kit
Spanish Factor de Células Madre, Factor de Crecimiento de Mastocitos, Factor de Célula Madre, Factor de Acero, Factor de Crecimiento de Mastocito, Ligando c-kit
Finnish Kantasolutekijä
French Facteur de cellule souche, Facteur de croissance du mastocyte, Ligand kit, Facteur de croissance SCF, Facteur de croissance mastocytaire, Facteur des cellules souches, Ligand de c-kit, Facteur steel, Ligand de kit, Ligand c-kit
Russian FAKTOR ROSTA STVOLOVYKH KLETOK KROVI, STVOLOVYKH KLETOK KROVI FAKTOR ROSTA, TUCHNYKH KLETOK FAKTOR ROSTA, СТВОЛОВЫХ КЛЕТОК КРОВИ ФАКТОР РОСТА, ТУЧНЫХ КЛЕТОК ФАКТОР РОСТА, ФАКТОР РОСТА СТВОЛОВЫХ КЛЕТОК КРОВИ
Italian Steel factor, Fattore di crescita delle mast-cellule, Ligando c-kit, Ligando kit, Fattore della cellula staminale
Polish Czynnik wzrostu komórek pnia, SCF, Czynnik wzrostu komórek macierzystych
Japanese 幹細胞因子, c-Kitリガンド, スチール因子, 肥満細胞成長因子, c-kitリガンド

Ontology: Stem Cell Factor (KIT) Receptor Inhibitors [MoA] (C2267146)

Concepts Molecular Function (T044)
English Stem Cell Factor (KIT) Receptor Inhibitors, Stem Cell Factor (KIT) Receptor Inhibitors [MoA], Stem Cell Factor (KIT) Inhibitors

Ontology: C-kit gene mutation (C3266990)

Concepts Cell or Molecular Dysfunction (T049)
English C-kit gene mutation
Czech Mutace genu C-kit
Dutch cKit-genmutatie
French Mutation du gène C-kit
German C-kit-Gen-Mutation
Hungarian C-kit génmutáció
Italian Mutazione del gene c-kit
Spanish Mutación en el gen C-kit
Japanese C−kit遺伝子突然変異, Ckitイデンシトツゼンヘンイ
Portuguese Mutação no gene C-kit