Journal ArticleDOI
Effect of the Tyrosine Kinase Inhibitor STI571 in a Patient with a Metastatic Gastrointestinal Stromal Tumor
Heikki Joensuu,Peter J. Roberts,Maarit Sarlomo-Rikala,Leif C. Andersson,Pekka Tervahartiala,David A. Tuveson,David A. Tuveson,Sandra Silberman,Renaud Capdeville,Sasa Dimitrijevic,Brian J. Druker,George D. Demetri +11 more
TLDR
Gastrointestinal stromal tumors are a group of mesenchymal neoplasms that arise from precursors of the connective-tissue cells of the gastrointestinal tract that occur predominantly in middle-aged and older persons.Abstract:
Gastrointestinal stromal tumors are a group of mesenchymal neoplasms that arise from precursors of the connective-tissue cells of the gastrointestinal tract.1 They occur predominantly in middle-aged and older persons, and approximately 70 percent of the tumors are found in the stomach, 20 to 30 percent are found in the small intestine, and less than 10 percent are found elsewhere in the gastrointestinal tract.1 Recent studies have shown that cells in gastrointestinal stromal tumors express a growth factor receptor with tyrosine kinase activity termed c-kit. This receptor, the product of the proto-oncogene c-kit, can be detected by immunohistochemical staining for . . .read more
Citations
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Journal ArticleDOI
Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.
George D. Demetri,Margaret von Mehren,Charles D. Blanke,Annick D. Van den Abbeele,Burton L. Eisenberg,Peter J. Roberts,Michael Heinrich,David A. Tuveson,Samuel Singer,Milos J. Janicek,Jonathan A. Fletcher,Stuart G. Silverman,Sandra Silberman,Renaud Capdeville,Beate Kiese,Bin Peng,Sasa Dimitrijevic,Brian J. Druker,Christopher L. Corless,Christopher D.M. Fletcher,Heikki Joensuu +20 more
TL;DR: Imatinib induced a sustained objective response in more than half of patients with an advanced unresectable or metastatic gastrointestinal stromal tumor, indicating that inhibition of the KIT signal-transduction pathway is a promising treatment for advanced gastrointestinalStromal tumors, which resist conventional chemotherapy.
Journal ArticleDOI
Oncogenic kinase signalling
Peter Blume-Jensen,Tony Hunter +1 more
TL;DR: How oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity is emphasized and an update is provided on the role of deregulated PI(3)K/Akt and mammalian target of rapamycin/p70S6K signalling in human malignancies.
Journal ArticleDOI
A quantitative analysis of kinase inhibitor selectivity.
Mazen W. Karaman,Sanna Herrgard,Daniel K. Treiber,Paul Gallant,Corey E. Atteridge,Brian T. Campbell,Katrina W Chan,Pietro Ciceri,Mindy I. Davis,Philip T. Edeen,Raffaella Faraoni,Mark Floyd,Jeremy P. Hunt,Daniel J Lockhart,Zdravko V. Milanov,Michael J Morrison,Gabriel Pallares,Hitesh K. Patel,Stephanie Pritchard,Stephanie Pritchard,Lisa M. Wodicka,Patrick P. Zarrinkar +21 more
TL;DR: This work presents interaction maps for 38 kinase inhibitors across a panel of 317 kinases representing >50% of the predicted human protein kinome and introduces the concept of a selectivity score as a general tool to quantify and differentiate the observed interaction patterns.
Journal ArticleDOI
Kinase Mutations and Imatinib Response in Patients With Metastatic Gastrointestinal Stromal Tumor
Michael Heinrich,Christopher L. Corless,George D. Demetri,Charles D. Blanke,Margaret von Mehren,Heikki Joensuu,Laura McGreevey,Chang Jie Chen,Annick D. Van den Abbeele,Brian J. Druker,Beate Kiese,Burton L. Eisenberg,Peter J. Roberts,Samuel Singer,Christopher D.M. Fletcher,Sandra Silberman,Sasa Dimitrijevic,Jonathan A. Fletcher +17 more
TL;DR: Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the mutational status of these oncoproteins is predictive of clinical response to imatinib.
Journal ArticleDOI
Protein kinases--the major drug targets of the twenty-first century?
TL;DR: A personal view of some of the most important advances that have shaped this field of protein kinases, after G-protein-coupled receptors.
References
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Journal ArticleDOI
Efficacy and Safety of a Specific Inhibitor of the BCR-ABL Tyrosine Kinase in Chronic Myeloid Leukemia
Brian J. Druker,Moshe Talpaz,Debra Resta,Bin Peng,Elisabeth Buchdunger,John Ford,Nicholas B. Lydon,Hagop M. Kantarjian,Renaud Capdeville,Sayuri Ohno-Jones,Charles L. Sawyers +10 more
TL;DR: STI571 is well tolerated and has significant antileukemic activity in patients with CML in whom treatment with interferon alfa had failed and demonstrates the potential for the development of anticancer drugs based on the specific molecular abnormality present in a human cancer.
Journal ArticleDOI
Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors.
Seiichi Hirota,Koji Isozaki,Yasuhiro Moriyama,Koji Hashimoto,Toshirou Nishida,Shingo Ishiguro,Kiyoshi Kawano,Masato Hanada,Akihiko Kurata,Masashi Takeda,Ghulam Muhammad Tunio,Yuji Matsuzawa,Yuzuru Kanakura,Yasuhisa Shinomura,Yukihiko Kitamura +14 more
TL;DR: Sequencing of c-kit complementary DNA from five GISTs revealed mutations in the region between the transmembrane and tyrosine kinase domains, suggesting that the mutations contribute to tumor development.
Journal ArticleDOI
Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells.
Brian J. Druker,Shu Tamura,Elisabeth Buchdunger,Sayuri Ohno,Gerald M. Segal,Shane Fanning,Jürg Zimmermann,Nicholas B. Lydon +7 more
TL;DR: A compound, designed to inhibit the Abl protein tyrosine kinase, was evaluated for its effects on cells containing the Bcr–Abl fusion protein and it was found that this compound may be useful in the treatment of bcr–abl–positive leukemias.
Journal ArticleDOI
Stem cell factor is encoded at the SI locus of the mouse and is the ligand for the c-kit tyrosine kinase receptor
Krisztina M. Zsebo,David A. Williams,Edwin N. Geissler,Virginia C. Broudy,Francis Hall Martin,Harry L. Atkins,Rou Yin Hsu,Neal C. Birkett,Kenneth H. Okino,Murdock Douglas C,Frederick W. Jacobsen,Keith Langley,Kent A. Smith,Takashi Takeish,Bruce M. Cattanach,Stephen J. Galli,Sidney Vaughn Suggs +16 more
TL;DR: In vivo administration of SCF can reverse the macrocytic anemia and locally repair the mast cell deficiency of Sl/Sld mice and provide biological and physical evidence that SCF is a ligand for the c-kit receptor.
Journal ArticleDOI
Gastrointestinal stromal tumors: recent advances in understanding of their biology.
Markku Miettinen,Markku Miettinen,Maarit Sarlomo-Rikala,Maarit Sarlomo-Rikala,Jerzy Lasota,Jerzy Lasota +5 more
TL;DR: The cell of origin is not fully understood, but resemblance to the interstitial cells of Cajal, expression of some smooth muscle markers, and occurrence outside of the GI-tract suggest origin from multipotential cells that can differentiate into Cjal and smooth muscle cells.
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Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors.
George D. Demetri,Margaret von Mehren,Charles D. Blanke,Annick D. Van den Abbeele,Burton L. Eisenberg,Peter J. Roberts,Michael Heinrich,David A. Tuveson,Samuel Singer,Milos J. Janicek,Jonathan A. Fletcher,Stuart G. Silverman,Sandra Silberman,Renaud Capdeville,Beate Kiese,Bin Peng,Sasa Dimitrijevic,Brian J. Druker,Christopher L. Corless,Christopher D.M. Fletcher,Heikki Joensuu +20 more