AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance
Thomas O'Hare,Thomas O'Hare,William C. Shakespeare,Xiaotian Zhu,Christopher A. Eide,Christopher A. Eide,Victor M. Rivera,Frank Wang,Lauren T. Adrian,Lauren T. Adrian,Tianjun Zhou,Huang Wei Sheng,Qihong Xu,Chester A. Metcalf,Jeffrey W. Tyner,Marc M. Loriaux,Amie S. Corbin,Amie S. Corbin,Scott Wardwell,Yaoyu Ning,Jeffrey A. Keats,Yihan Wang,Raji Sundaramoorthi,Mathew Thomas,Dong Zhou,Joseph Snodgrass,Lois Commodore,Tomi K. Sawyer,David C. Dalgarno,Michael W. Deininger,Brian J. Druker,Brian J. Druker,Tim Clackson +32 more
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TLDR
Design and preclinical evaluation of AP24534, a potent, orally available multitargeted kinase inhibitor active against T315I and other BCR-ABL mutants, and clinical evaluation ofAP24534 as a pan-BCR-ABl inhibitor for treatment of CML are reported.About:
This article is published in Cancer Cell.The article was published on 2009-11-03 and is currently open access. It has received 1075 citations till now. The article focuses on the topics: Dasatinib & Nilotinib.read more
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Cancer drug resistance: an evolving paradigm
TL;DR: There are now unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive biomarkers to enable patient stratification.
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European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013
Michele Baccarani,Michael W. Deininger,Gianantonio Rosti,Andreas Hochhaus,Simona Soverini,Jane F. Apperley,Francisco Cervantes,Richard E. Clark,Jorge E. Cortes,François Guilhot,Henrik Hjorth-Hansen,Timothy P. Hughes,Hagop M. Kantarjian,Dong-Wook Kim,Richard A. Larson,Jeffrey H. Lipton,François Xavier Mahon,Giovanni Martinelli,Jiri Mayer,Martin C. Müller,Dietger Niederwieser,Fabrizio Pane,Jerald P. Radich,Philippe Rousselot,Giuseppe Saglio,Susanne Saußele,Charles A. Schiffer,Richard T. Silver,Bengt Simonsson,Juan Luis Steegmann,John M. Goldman,Rüdiger Hehlmann +31 more
TL;DR: Optimal responders to chronic myeloid leukemia treatment should continue therapy indefinitely, with careful surveillance, or they can be enrolled in controlled studies of treatment discontinuation once a deeper molecular response is achieved.
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Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling.
Nikhil Wagle,Caroline Emery,Michael F. Berger,Matthew J. Davis,Allison M. Sawyer,Panisa Pochanard,Sarah M. Kehoe,Cory M. Johannessen,Laura E. MacConaill,William C. Hahn,Matthew Meyerson,Levi A. Garraway +11 more
TL;DR: The MEK1(C121S) mutation was shown to increase kinase activity and confer robust resistance to both RAF and MEK inhibition in vitro, and the use of emerging technologies in a manner that may accelerate personalized cancer medicine is illustrated.
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A Phase 2 Trial of Ponatinib in Philadelphia Chromosome–Positive Leukemias
Jorge E. Cortes,Dong-Kee Kim,Javier Pinilla-Ibarz,P. le Coutre,Ronald Paquette,Charles Chuah,F. E. Nicolini,Jane F. Apperley,Hanna Jean Khoury,Moshe Talpaz,John F. DiPersio,Daniel J. DeAngelo,Elisabetta Abruzzese,Delphine Rea,Michele Baccarani,Martin C. Müller,Carlo Gambacorti-Passerini,Stephane Wong,Stephanie Lustgarten,Victor M. Rivera,Timothy P. Clackson,Christopher D. Turner,Frank G. Haluska,François Guilhot,Michael W. Deininger,Andreas Hochhaus,Timothy P. Hughes,J. M. Goldman,Neil P. Shah,Hagop M. Kantarjian +29 more
TL;DR: Ponatinib had significant antileukemic activity across categories of disease stage and mutation status and were durable; the estimated rate of a sustained major cytogenetic response of at least 12 months was 91%.
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NTRK fusion-positive cancers and TRK inhibitor therapy
TL;DR: TRK fusion proteins are pathognomonic in certain rare tumour types and present in a small subset of diverse cancer types, including some common cancers; TRK inhibitors have promising efficacy in the treatment of these cancers, in a histology-agnostic manner.
References
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