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CDK6-DrugOpp SIGNED

CDK6 in transcription - turning a foe in a friend

Total Cost €

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EC-Contrib. €

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Partnership

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 CDK6-DrugOpp project word cloud

Explore the words cloud of the CDK6-DrugOpp project. It provides you a very rough idea of what is the project "CDK6-DrugOpp" about.

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Project "CDK6-DrugOpp" data sheet

The following table provides information about the project.

Coordinator
VETERINAERMEDIZINISCHE UNIVERSITAET WIEN 

Organization address
address: Veterinaerplatz 1
city: VIENNA
postcode: 1210
website: www.vetmeduni.ac.at

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Austria [AT]
 Total cost 2˙497˙520 €
 EC max contribution 2˙497˙520 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VETERINAERMEDIZINISCHE UNIVERSITAET WIEN AT (VIENNA) coordinator 2˙497˙520.00

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 Project objective

'Translational research aims at applying mechanistic understanding in the development of 'precision medicine', which depends on precise diagnostic tools and therapeutic approaches. Cancer therapy is experiencing a switch from non-specific, cytotoxic agents towards molecularly targeted and rationally designed compounds with the promise of greater efficacy and fewer side effects.

The two cell-cycle kinases CDK4 and CDK6 normally facilitate cell-cycle progression but are abnormally activated in certain cancers. CDK6 is up-regulated in hematopoietic malignancies, where it is the predominant cell-cycle kinase. The importance of CDK4/6 for tumor development is underscored by the fact that the US FDA selected inhibitors of the kinase activity of CDK4/6 as 'breakthrough of the year 2013'. Our recent findings suggest that the effects of the inhibitors may be limited as CDK6 is not only involved in cell-cycle progression: ground-breaking research in my group and others has shown that CDK6 is involved in regulation of transcription in a kinase-independent manner thereby driving the proliferation of leukemic stem cells and tumor formation. We have now identified mutations in CDK6 that convert it from a tumor promoter into a tumor suppressor. This unexpected outcome is accompanied by a distinct transcriptional profile. Separating the tumor-promoting from the tumor suppressive functions may open a novel therapeutic avenue for drug development. We aim at understanding which domains and residues of CDK6 are involved in rewiring the transcriptional landscape to pave the way for sophisticated inhibitors. The idea of turning a cancer cell's own most potent weapon against itself is novel and would represent a new paradigm for drug design. Finally, the understanding of CDK6 functions in tumor promotion and maintenance will also result in better patient stratification and improved treatment decisions for a broad spectrum of cancer types.'

 Publications

year authors and title journal last update
List of publications.
2019 Iris Z. Uras, Barbara Maurer, Harini Nivarthi, Philipp Jodl, Karoline Kollmann, Michaela Prchal-Murphy, Jelena D. Milosevic Feenstra, Markus Zojer, Sabine Lagger, Reinhard Grausenburger, Beatrice Grabner, Raimund Holly, Anoop Kavirayani, Christoph Bock, Heinz Gisslinger, Peter Valent, Robert Kralovics, Veronika Sexl
CDK6 coordinates JAK2 V617F mutant MPN via NF-κB and apoptotic networks
published pages: 1677-1690, ISSN: 0006-4971, DOI: 10.1182/blood-2018-08-872648
Blood 133/15 2019-09-02
2018 Iris Uras, Barbara Maurer, Sofie Nebenfuehr, Markus Zojer, Peter Valent, Veronika Sexl
Therapeutic Vulnerabilities in FLT3-Mutant AML Unmasked by Palbociclib
published pages: 3987, ISSN: 1422-0067, DOI: 10.3390/ijms19123987
International Journal of Molecular Sciences 19/12 2019-08-30
2017 Iris Z Uras, Florian Bellutti, Veronika Sexl
p27 in FLT3-driven acute myeloid leukemia: many roads lead to ruin
published pages: 1299-1301, ISSN: 0390-6078, DOI: 10.3324/haematol.2017.171819
Haematologica 102/8 2019-06-13
2017 Iris Z. Uras, Ruth M. Scheicher, Karoline Kollmann, Martin Glösmann, Michaela Prchal-Murphy, Anca S. Tigan, Daniela A. Fux, Sandro Altamura, Joana Neves, Martina U. Muckenthaler, Keiryn L. Bennett, Stefan Kubicek, Philip W. Hinds, Marieke von Lindern, Veronika Sexl
Cdk6 contributes to cytoskeletal stability in erythroid cells
published pages: 995-1005, ISSN: 0390-6078, DOI: 10.3324/haematol.2016.159947
Haematologica 102/6 2019-06-13
2018 Sofie Nebenfuehr, Florian Bellutti, Veronika Sexl
Cdk6: At the interface of Rb and p53
published pages: e1511206, ISSN: 2372-3556, DOI: 10.1080/23723556.2018.1511206
Molecular & Cellular Oncology 5/5 2019-05-08
2018 Florian Bellutti, Anca-Sarmiza Tigan, Sofie Nebenfuehr, Marlies Dolezal, Markus Zojer, Reinhard Grausenburger, Svenja Hartenberger, Sebastian Kollmann, Eszter Doma, Michaela Prchal-Murphy, Iris Z. Uras, Alexander Höllein, Donna S. Neuberg, Benjamin L. Ebert, Anna Ringler, Andre C. Mueller, Joanna I. Loizou, Philip W. Hinds, Claus Vogl, Gerwin Heller, Stefan Kubicek, Johannes Zuber, Marcos Malumbres, Matthias Farlik, Andreas Villunger, Karoline Kollmann, Veronika Sexl
CDK6 Antagonizes p53-Induced Responses during Tumorigenesis
published pages: 884-897, ISSN: 2159-8274, DOI: 10.1158/2159-8290.CD-17-0912
Cancer Discovery 8/7 2019-05-08

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