title: Tyrosine kinase gene rearrangements in epithelial malignancies.
abstract: Chromosomal rearrangements that lead to oncogenic kinase activation are observed in many epithelial cancers. These cancers express activated fusion kinases that drive the initiation and progression of malignancy, and often have a considerable response to small-molecule kinase inhibitors, which validates these fusion kinases as 'druggable' targets. In this Review, we examine the aetiologic, pathogenic and clinical features that are associated with cancers harbouring oncogenic fusion kinases, including anaplastic lymphoma kinase (ALK), ROS1 and RET. We discuss the clinical outcomes with targeted therapies and explore strategies to discover additional kinases that are activated by chromosomal rearrangements in solid tumours.
authors.affiliation: Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, USA.
authors.forename: Alice T
authors.initials: AT
authors.lastname: Shaw
authors.forename: Peggy P
authors.initials: PP
authors.lastname: Hsu
authors.forename: Mark M
authors.initials: MM
authors.lastname: Awad
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Engelman
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D004777:Environment; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D005819:Genetic Markers; D006801:Humans; D051379:Mice; D009375:Neoplasms, Glandular and Epithelial / Q000201:enzymology* / Q000235:genetics*; D009381:Neoplasms, Radiation-Induced / Q000235:genetics; D009857:Oncogenes; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics
chemical_list: D005819:Genetic Markers; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases