Literature DB >> 20418915

Targeting mTOR: prospects for mTOR complex 2 inhibitors in cancer therapy.

C A Sparks1, D A Guertin.   

Abstract

Small molecule inhibitors that selectively target cancer cells and not normal cells would be valuable anti-cancer therapeutics. The mammalian target of rapamycin complex 2 (mTORC2) is emerging as a promising candidate target for such an inhibitor. Recent studies in cancer biology indicate that mTORC2 activity is essential for the transformation and vitality of a number of cancer cell types, but in many normal cells, mTORC2 activity is less essential. These studies are intensifying interest in developing inhibitors that specifically target mTORC2. However, there are many open questions regarding the function and regulation of mTORC2 and its function in both normal and cancer cells. Here, we summarize exciting new research into the biology of mTORC2 signaling and highlight the current state and future prospects for mTOR-targeted therapy.

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Year:  2010        PMID: 20418915      PMCID: PMC3031870          DOI: 10.1038/onc.2010.139

Source DB:  PubMed          Journal:  Oncogene        ISSN: 0950-9232            Impact factor:   9.867


  103 in total

1.  GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR.

Authors:  Do-Hyung Kim; D D Sarbassov; Siraj M Ali; Robert R Latek; Kalyani V P Guntur; Hediye Erdjument-Bromage; Paul Tempst; David M Sabatini
Journal:  Mol Cell       Date:  2003-04       Impact factor: 17.970

2.  Crystal structure of an activated Akt/protein kinase B ternary complex with GSK3-peptide and AMP-PNP.

Authors:  Jing Yang; Peter Cron; Valerie M Good; Vivienne Thompson; Brian A Hemmings; David Barford
Journal:  Nat Struct Biol       Date:  2002-12

3.  Mechanism of activation of protein kinase B by insulin and IGF-1.

Authors:  D R Alessi; M Andjelkovic; B Caudwell; P Cron; N Morrice; P Cohen; B A Hemmings
Journal:  EMBO J       Date:  1996-12-02       Impact factor: 11.598

4.  The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif.

Authors:  Hiroki Nojima; Chiharu Tokunaga; Satoshi Eguchi; Noriko Oshiro; Sujuti Hidayat; Ken-ichi Yoshino; Kenta Hara; Noriaki Tanaka; Joseph Avruch; Kazuyoshi Yonezawa
Journal:  J Biol Chem       Date:  2003-02-25       Impact factor: 5.157

5.  Disruption of the mouse mTOR gene leads to early postimplantation lethality and prohibits embryonic stem cell development.

Authors:  Yann-Gaël Gangloff; Matthias Mueller; Stephen G Dann; Petr Svoboda; Melanie Sticker; Jean-Francois Spetz; Sung Hee Um; Eric J Brown; Silvia Cereghini; George Thomas; Sara C Kozma
Journal:  Mol Cell Biol       Date:  2004-11       Impact factor: 4.272

6.  mTOR is essential for growth and proliferation in early mouse embryos and embryonic stem cells.

Authors:  Mirei Murakami; Tomoko Ichisaka; Mitsuyo Maeda; Noriko Oshiro; Kenta Hara; Frank Edenhofer; Hiroshi Kiyama; Kazuyoshi Yonezawa; Shinya Yamanaka
Journal:  Mol Cell Biol       Date:  2004-08       Impact factor: 4.272

7.  The in vivo role of PtdIns(3,4,5)P3 binding to PDK1 PH domain defined by knockin mutation.

Authors:  Edward J McManus; Barry J Collins; Peter R Ashby; Alan R Prescott; Victoria Murray-Tait; Laura J Armit; J Simon C Arthur; Dario R Alessi
Journal:  EMBO J       Date:  2004-04-29       Impact factor: 11.598

8.  Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton.

Authors:  D D Sarbassov; Siraj M Ali; Do-Hyung Kim; David A Guertin; Robert R Latek; Hediye Erdjument-Bromage; Paul Tempst; David M Sabatini
Journal:  Curr Biol       Date:  2004-07-27       Impact factor: 10.834

9.  TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function.

Authors:  Stefanie S Schalm; Diane C Fingar; David M Sabatini; John Blenis
Journal:  Curr Biol       Date:  2003-05-13       Impact factor: 10.834

10.  Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton.

Authors:  Anjon Audhya; Robbie Loewith; Ainslie B Parsons; Lu Gao; Mitsuaki Tabuchi; Huilin Zhou; Charles Boone; Michael N Hall; Scott D Emr
Journal:  EMBO J       Date:  2004-09-16       Impact factor: 11.598

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  141 in total

1.  Oncogenic EGFR signaling activates an mTORC2-NF-κB pathway that promotes chemotherapy resistance.

Authors:  Kazuhiro Tanaka; Ivan Babic; David Nathanson; David Akhavan; Deliang Guo; Beatrice Gini; Julie Dang; Shaojun Zhu; Huijun Yang; Jason De Jesus; Ali Nael Amzajerdi; Yinan Zhang; Christian C Dibble; Hancai Dan; Amanda Rinkenbaugh; William H Yong; Harry V Vinters; Joseph F Gera; Webster K Cavenee; Timothy F Cloughesy; Brendan D Manning; Albert S Baldwin; Paul S Mischel
Journal:  Cancer Discov       Date:  2011-09-13       Impact factor: 39.397

2.  mTOR kinase inhibition causes feedback-dependent biphasic regulation of AKT signaling.

Authors:  Vanessa S Rodrik-Outmezguine; Sarat Chandarlapaty; Nen C Pagano; Poulikos I Poulikakos; Maurizio Scaltriti; Elizabeth Moskatel; José Baselga; Sylvie Guichard; Neal Rosen
Journal:  Cancer Discov       Date:  2011-06-17       Impact factor: 39.397

Review 3.  Emergence of the PI3-kinase pathway as a central modulator of normal and aberrant B cell differentiation.

Authors:  G V Baracho; A V Miletic; S A Omori; M H Cato; R C Rickert
Journal:  Curr Opin Immunol       Date:  2011-02-01       Impact factor: 7.486

Review 4.  Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells.

Authors:  Shanchun Guo; Mingli Liu; Guangdi Wang; Marta Torroella-Kouri; Ruben R Gonzalez-Perez
Journal:  Biochim Biophys Acta       Date:  2012-01-24

5.  Targeting of mTORC2 may have advantages over selective targeting of mTORC1 in the treatment of malignant pheochromocytoma.

Authors:  Xiaohua Zhang; Xianjin Wang; Tianyuan Xu; Shan Zhong; Zhoujun Shen
Journal:  Tumour Biol       Date:  2015-02-11

6.  Dual mTORC1/mTORC2 blocker as a possible therapy for tauopathy in cellular model.

Authors:  Mohamed Salama; Mahmoud Elhussiny; Alshimaa Magdy; Ahmed G Omran; Aziza Alsayed; Ramy Ashry; Wael Mohamed
Journal:  Metab Brain Dis       Date:  2017-10-27       Impact factor: 3.584

Review 7.  Differentiating mTOR inhibitors in renal cell carcinoma.

Authors:  Sumanta K Pal; David I Quinn
Journal:  Cancer Treat Rev       Date:  2013-02-21       Impact factor: 12.111

Review 8.  mTOR: a pharmacologic target for autophagy regulation.

Authors:  Young Chul Kim; Kun-Liang Guan
Journal:  J Clin Invest       Date:  2015-01-02       Impact factor: 14.808

Review 9.  The multifaceted role of mTORC1 in the control of lipid metabolism.

Authors:  Stéphane J H Ricoult; Brendan D Manning
Journal:  EMBO Rep       Date:  2012-02-12       Impact factor: 8.807

10.  Gonadotropin releasing hormone activation of the mTORC2/Rictor complex regulates actin remodeling and ERK activity in LβT2 cells.

Authors:  Brian S Edwards; William J Isom; Amy M Navratil
Journal:  Mol Cell Endocrinol       Date:  2016-09-20       Impact factor: 4.102

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