Imatinib mesylate is a chemotherapeutic drug that inhibits the tyrosine kinase activity of c-KIT and has been successfully used to treat leukemias and some solid tumors.
They have represented a paradigm of molecular-targeted therapies for solid tumors since the discovery of KIT mutations and KIT expression in GIST in 1998, which opened the way to the use of imatinib, a tyrosine kinase inhibitor able to inhibit the growth of cells expressing KIT-mutant isoforms.
Sunitinib is a clinically approved multitargeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor, c-KIT, and PDGFR, and has shown clinical activity in various solid tumors.
Notably, most pediatric KIT-wild-type GISTs progress to malignancy without acquiring large-scale chromosomal aberrations, which is a phenomenon not reported previously in malignant solid tumors.
We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the c-kit and PDGFR tyrosine kinases, on the growth of rodent Leydig tumor cell lines in vivo and in vitro, and examined, in human Leydig cell tumor samples, the expression of activated PDGFR and c-kit and the mutations in exons of the c-kit gene commonly associated with solid tumors.
The tyrosine-kinase receptor c-kit (CD117) and its ligand stem cell factor are considered to be co-expressed in various solid tumors, including adenocarcinomas of the lung.
The results suggest that the c-kit gene products may be involved in the pathogenesis of a very restricted subset of human solid tumors such as small cell lung cancer.
These data show that some human solid tumor cell lines display high-affinity c-kit receptors and produce SCF, which can be detected on the cell surface.