title: Tyrosine kinase mutations in human cancer.
abstract: A subset of tyrosine kinases are activated by mutations which contribute to the malignant transformation, growth, and metastasis of human cancers. Mutations change the expression, conformation and/or stability of tyrosine kinases, often leading to constitutive activation of the signaling pathways the kinases regulate. Given that tyrosine kinases are key members of signaling cascades, mutations have multiple effects on various cellular proteins. This review will focus on four kinases (EGFR, c-Met, c-Kit, and PI3-kinase) known to be mutated in human cancer. It will discuss the effects that these mutations have on the biology of tumors, and how our understanding of the structure and function of kinases and their mutations is currently being used to design targeted treatments.
authors.affiliation: University of Chicago, Department of Obstetrics and Gynecology, MC 2050, Section of Gynecologic Oncology, 5841 South Maryland Avenue, Chicago, IL 60637, USA. elengyel@uchicago.edu
authors.forename: Ernst
authors.initials: E
authors.lastname: Lengyel
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Sawada
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
mesh_terms: D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000628:therapy; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D019859:Proto-Oncogene Proteins c-met