[Gastrointestinal stromal tumors: evolution of a tumor concept from unclassifiable neoplasms to targeted molecular therapy].
The discovery of activating oncogenic C-KIT and PDGFRA mutations in gastrointestinal stromal tumors (GIST) represented the key for the development of innovative targeted molecular therapy using the tyrosine kinase inhibitors (TKI) Imatinib (Glivec(R)), Sunitinib and other substances. This makes a precise histopathological diagnosis a major prerequisite, supplemented by appropriate risk stratification for the assessment of the expected biological behavior of individual tumors. Current knowledge demonstrates that the presence of kinase mutations in C-KIT and PDGFRA and their localization within the gene sequence as well as the mutation type are of great importance for planning appropriate treatment (drug selection and dose recommendation), but also for the assessment of prognosis and explanation of secondary resistance to TKI after initial response. This article gives an overview on current developments in the histopathological and molecular diagnostics of GIST and the role of kinase mutation analysis for optimizing patient treatment.
Agaimy
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Pathologisches Institut, Universitätsklinikum Erlangen, Krankenhausstr. 12, 91054, Erlangen, Deutschland. abbas.agaimy@uk-erlangen.de
Schneider-Stock
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D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D004252:DNA Mutational Analysis; D016503:Drug Delivery Systems; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D041981:Gastrointestinal Tract / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D017422:Sequence Analysis, DNA; D000077210:Sunitinib
D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D011743:Pyrimidines; D011758:Pyrroles; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit; D020796:Receptor, Platelet-Derived Growth Factor alpha; D000077210:Sunitinib