Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF
Sonja J. Heidorn,Carla Milagre,Steven R. Whittaker,Arnaud Nourry,Ion Niculescu-Duvas,Nathalie Dhomen,Jahan Hussain,Jorge S. Reis-Filho,Caroline J. Springer,Catrin Pritchard,Richard Marais +10 more
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TLDR
It is shown that drugs that selectively inhibit BRAF drive RAS-dependent BRAF binding to CRAF, CRAF activation, and MEK–ERK signaling, demonstrating that BRAF inhibition per se does not drive pathway activation; it only occurs when BRAF is inhibited in the presence of oncogenic RAS.About:
This article is published in Cell.The article was published on 2010-01-22 and is currently open access. It has received 1343 citations till now. The article focuses on the topics: Encorafenib.read more
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Journal ArticleDOI
Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation
Paul B. Chapman,Axel Hauschild,Caroline Robert,John B. A. G. Haanen,Paolo A. Ascierto,James Larkin,Reinhard Dummer,Claus Garbe,Alessandro Testori,Michele Maio,David W. Hogg,Paul Lorigan,Céleste Lebbé,Thomas Jouary,Dirk Schadendorf,Antoni Ribas,Jeffrey A. Sosman,John M. Kirkwood,Brigitte Dréno,K. B. Nolop,Jiang Li,B. Nelson,Jeannie Hou,Richard J. Lee,Keith T. Flaherty,Grant A. McArthur +25 more
TL;DR: Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation in a phase 3 randomized clinical trial.
Journal ArticleDOI
Inhibition of mutated, activated BRAF in metastatic melanoma.
Keith T. Flaherty,Igor Puzanov,Kevin B. Kim,Antoni Ribas,Grant A. McArthur,Jeffrey A. Sosman,Peter J. O'Dwyer,Richard J. Lee,Joseph F. Grippo,K. B. Nolop,Paul B. Chapman +10 more
TL;DR: Treatment of metastatic melanoma with PLX4032 in patients with tumors that carry the V600E BRAF mutation resulted in complete or partial tumor regression in the majority of patients.
Journal ArticleDOI
Combined BRAF and MEK Inhibition in Melanoma with BRAF V600 Mutations
Keith T. Flaherty,J. R. Infante,Adil Daud,Rene Gonzalez,Richard F. Kefford,Jeffrey A. Sosman,Omid Hamid,Lynn M. Schuchter,Jonathan Cebon,Nageatte Ibrahim,Ragini Kudchadkar,Howard A. Burris,Gerald S. Falchook,Alain Algazi,Karl D. Lewis,Georgina V. Long,Igor Puzanov,Peter F. Lebowitz,Ajay Singh,Shonda M Little,Peng Sun,Alicia Allred,Daniele Ouellet,Kevin B. Kim,Kiran Patel,Jeffrey S. Weber +25 more
TL;DR: Dabrafenib and trametinib were safely combined at full monotherapy doses, and the rate of pyrexia was increased with combination therapy, whereas the rates of proliferative skin lesions was nonsignificantly reduced.
Journal ArticleDOI
Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
Ramin Nazarian,Hubing Shi,Qi Wang,Xiangju Kong,Richard C. Koya,Hane Lee,Zugen Chen,Mi Kyung Lee,Narsis Attar,Hooman Sazegar,Thinle Chodon,Stanley F. Nelson,Grant A. McArthur,Jeffrey A. Sosman,Antoni Ribas,Roger S. Lo +15 more
TL;DR: It is shown that melanomas escape B-RAF(V600E) targeting not through secondary B-RF(V 600E) mutations but via receptor tyrosine kinase (RTK)-mediated activation of alternative survival pathway(s) or activated RAS-mediated reactivation of the MAPK pathway, suggesting additional therapeutic strategies.
Journal ArticleDOI
Survival in BRAF V600–Mutant Advanced Melanoma Treated with Vemurafenib
Jeffrey A. Sosman,Kevin B. Kim,Lynn M. Schuchter,Rene Gonzalez,Anna C. Pavlick,Jeffrey S. Weber,Grant A. McArthur,Thomas E. Hutson,Stergios J. Moschos,Keith T. Flaherty,Peter Hersey,Richard F. Kefford,Donald P. Lawrence,Igor Puzanov,Karl D. Lewis,Ravi K. Amaravadi,Bartosz Chmielowski,H. Jeffrey Lawrence,Yu Shyr,Fei Ye,Jiang Li,K. B. Nolop,Richard J. Lee,Andrew K. Joe,Antoni Ribas +24 more
TL;DR: Vemurafenib induces clinical responses in more than half of patients with previously treated BRAF V600-mutant metastatic melanoma, and the median overall survival in this study with a long follow-up was approximately 16 months.
References
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TL;DR: It is shown that the use of a recombinant adenovirus expressing Cre recombinase (AdenoCre) to induce K-ras G12D expression in the lungs of mice allows control of the timing and multiplicity of tumor initiation.
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