Direct reversal of glucocorticoid resistance by AKT inhibition in acute lymphoblastic leukemia
Erich Piovan,Erich Piovan,Jiyang Yu,Valeria Tosello,Daniel Herranz,Alberto Ambesi-Impiombato,Ana Carolina Da Silva,Marta Sanchez-Martin,Arianne Perez-Garcia,Isaura Rigo,Mireia Castillo,Stefano Indraccolo,Justin R. Cross,Elisa de Stanchina,Elisabeth Paietta,Elisabeth Paietta,Janis Racevskis,Janis Racevskis,Jacob M. Rowe,Martin S. Tallman,Giuseppe Basso,Jules P.P. Meijerink,Carlos Cordon-Cardo,Andrea Califano,Adolfo A. Ferrando +24 more
TLDR
It is demonstrated that loss of PTEN and consequent AKT1 activation can effectively block glucocorticoid-induced apoptosis and induce resistance to glucoc Corticoid therapy, and pharmacologic inhibition of AKT with MK2206 effectively reverses glucocORTicoid resistance.About:
This article is published in Cancer Cell.The article was published on 2013-12-09 and is currently open access. It has received 223 citations till now. The article focuses on the topics: Glucocorticoid receptor & Protein kinase B.read more
Citations
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Functional characterization of somatic mutations in cancer using network-based inference of protein activity
Mariano J. Alvarez,Yao Shen,Federico M. Giorgi,Alexander Lachmann,B. Belinda Ding,B. Hilda Ye,Andrea Califano +6 more
TL;DR: A fraction of tumors is identified with aberrant activity of druggable oncoproteins despite a lack of mutations, and vice versa, and in vitro assays confirmed that VIPER-inferred protein activity outperformed mutational analysis in predicting sensitivity to targeted inhibitors.
Journal ArticleDOI
The Varied Roles of Notch in Cancer
TL;DR: The varied roles of Notch in cancer are discussed, focusing on cell autonomous activities that may be either oncogenic or tumor suppressive.
Journal ArticleDOI
PTEN: Multiple Functions in Human Malignant Tumors
Michele Milella,Italia Falcone,Fabiana Conciatori,Ursula Cesta Incani,Anais Del Curatolo,Nicola Inzerilli,Carmen Nuzzo,Vanja Vaccaro,Sabrina Vari,Francesco Cognetti,Ludovica Ciuffreda +10 more
TL;DR: The current understanding of the biological role of PTEN, how PTEN expression and activity are regulated, and the consequences ofPTEN dysregulation in human malignant tumors are discussed.
Journal ArticleDOI
Pathway and network analysis of cancer genomes
Pau Creixell,Jueri Reimand,Syed Haider,Guanming Wu,Tatsuhiro Shibata,Miguel Vazquez,Ville Mustonen,Abel Gonzalez-Perez,John V. Pearson,Chris Sander,Rune Linding +10 more
TL;DR: An overview of pathway and network analysis methods that group genes and illuminate the processes involved in tumor biology are provided and where they guide mechanistic and translational investigations are shown.
Journal ArticleDOI
The genetics and mechanisms of T cell acute lymphoblastic leukaemia
Laura Belver,Adolfo A. Ferrando +1 more
TL;DR: The current understanding of the molecular mechanisms of T-ALL is examined and recent developments in the translation of these results to the clinic are examined.
References
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Journal ArticleDOI
Akt Phosphorylation of BAD Couples Survival Signals to the Cell-Intrinsic Death Machinery
Sandeep Robert Datta,Henryk Dudek,Xu Tao,Shane C. Masters,Haian Fu,Yukiko Gotoh,Michael E. Greenberg +6 more
TL;DR: It is shown that growth factor activation of the PI3'K/Akt signaling pathway culminates in the phosphorylation of the BCL-2 family member BAD, thereby suppressing apoptosis and promoting cell survival.
Journal ArticleDOI
Interleukin-3-Induced Phosphorylation of BAD Through the Protein Kinase Akt
Luis del Peso,Maribel González-García,Maribel González-García,Carmen Page,Carmen Page,Roman Herrera,Roman Herrera,Gabriel Núñez,Gabriel Núñez +8 more
TL;DR: The proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway, and active, but not inactive, forms of Akt were found to phosphorylate BAD in vivo and in vitro at the same residues that are phosphorylated in response to IL-3.
Journal ArticleDOI
NF-κB activation by tumour necrosis factor requires the Akt serine–threonine kinase
Osman N. Ozes,Lindsey D. Mayo,Jason A. Gustin,Susan R. Pfeffer,Lawrence M. Pfeffer,David B. Donner +5 more
TL;DR: It is shown that the Akt serine–threonine kinase is involved in the activation of NF-κB by tumour necrosis factor (TNF), and that Akt is part of a signalling pathway that is necessary for inducing key immune and inflammatory responses.
Journal ArticleDOI
Phosphorylation and Regulation of Raf by Akt (Protein Kinase B)
Sven Zimmermann,Karin Moelling +1 more
TL;DR: Observations provide a molecular basis for cross talk between two signaling pathways at the level of Raf and Akt in a human breast cancer cell line.
Journal ArticleDOI
MK-2206, an Allosteric Akt Inhibitor, Enhances Antitumor Efficacy by Standard Chemotherapeutic Agents or Molecular Targeted Drugs In vitro and In vivo
Hiroshi Hirai,Hiroshi Sootome,Yoko Nakatsuru,Katsuyoshi Miyama,Shunsuke Taguchi,Kyoko Tsujioka,Yoko Ueno,Harold Hatch,Pradip K. Majumder,Bo-Sheng Pan,Hidehito Kotani +10 more
TL;DR: It is suggested that Akt inhibition may augment the efficacy of existing cancer therapeutics; thus, MK-2206 is a promising agent to treat cancer patients who receive cytotoxic and/or molecular targeted agents.
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