N
Neal Rosen
Researcher at Memorial Sloan Kettering Cancer Center
Publications - 360
Citations - 49346
Neal Rosen is an academic researcher from Memorial Sloan Kettering Cancer Center. The author has contributed to research in topics: MAPK/ERK pathway & PI3K/AKT/mTOR pathway. The author has an hindex of 117, co-authored 350 publications receiving 44546 citations. Previous affiliations of Neal Rosen include University of California, Los Angeles & University of Washington.
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Journal ArticleDOI
mTOR Inhibition Induces Upstream Receptor Tyrosine Kinase Signaling and Activates Akt
Kathryn E. O'Reilly,Fredi Rojo,Qing-Bai She,David B. Solit,Gordon B. Mills,Debra G. Smith,Heidi Lane,Francesco Hofmann,Daniel J. Hicklin,Dale L. Ludwig,José Baselga,Neal Rosen +11 more
TL;DR: The data suggest that feedback down-regulation of receptor tyrosine kinase signaling is a frequent event in tumor cells with constitutive mTOR activation, and reversal of this feedback loop by rapamycin may attenuate its therapeutic effects, whereas combination therapy that ablates mTOR function and prevents Akt activation may have improved antitumor activity.
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RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF
TL;DR: Because RAF inhibitors do not inhibit ERK signalling in other cells, the model predicts that they would have a higher therapeutic index and greater antitumour activity than mitogen-activated protein kinase (MEK) inhibitors, but could also cause toxicity due to MEK/ERK activation.
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Crystal Structure of an Hsp90–Geldanamycin Complex: Targeting of a Protein Chaperone by an Antitumor Agent
TL;DR: The structure of the geldanamycin-binding domain of Hsp90 reveals a pronounced pocket that is highly conserved across species, and the pocket's similarity to substrate-binding sites suggest that the pocket binds a portion of the polypeptide substrate and participates in the conformational maturation/refolding reaction.
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RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)
Poulikos I. Poulikakos,Yogindra Persaud,Manickam Janakiraman,Xiangju Kong,Charles Ng,Gatien Moriceau,Hubing Shi,Mohammad Atefi,Bjoern Titz,May Tal Gabay,Maayan Salton,Kimberly B. Dahlman,Madhavi Tadi,Jennifer A. Wargo,Keith T. Flaherty,Mark C. Kelley,Tom Misteli,Paul B. Chapman,Jeffrey A. Sosman,Thomas G. Graeber,Antoni Ribas,Roger S. Lo,Neal Rosen,David B. Solit +23 more
TL;DR: The model that inhibition of ERK signalling by RAF inhibitors is dependent on levels of RAS–GTP too low to support RAF dimerization is supported and a novel mechanism of acquired resistance in patients is identified: expression of splicing isoforms of BRAF(V600E) that dimerize in a RAS-independent manner.
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BRAF mutation predicts sensitivity to MEK inhibition
David B. Solit,Levi A. Garraway,Levi A. Garraway,Christine A. Pratilas,Ayana Sawai,Gad Getz,Andrea D. Basso,Andrea D. Basso,Qing Ye,Jose Lobo,Yuhong She,Iman Osman,Todd R. Golub,Todd R. Golub,Judith Sebolt-Leopold,William R. Sellers,William R. Sellers,Neal Rosen +17 more
TL;DR: It is found that mutation of BRAF is associated with enhanced and selective sensitivity to MEK inhibition when compared to either ‘wild-type’ cells or cells harbouring a RAS mutation, suggesting an exquisite dependency on MEK activity in BRAF mutant tumours.