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BET and Aurora Kina...
BET and Aurora Kinase A inhibitors synergize against MYCN-positive human glioblastoma cells
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- Cancer, Matko (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Drews, Lisa F. (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Bengtsson, Johan (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab
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- Bolin, Sara, 1988- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi
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- Rosén, Gabriela (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi
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- Westermark, Bengt (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi
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- Nelander, Sven (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi
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- Forsberg Nilsson, Karin, 1963- (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi
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- Uhrbom, Lene (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi
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- Weishaupt, Holger (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi
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- Johansson, Fredrik K., 1975- (author)
- Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab
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(creator_code:org_t)
- 2019-11-21
- 2019
- English.
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In: Cell Death and Disease. - : NATURE PUBLISHING GROUP. - 2041-4889. ; 10
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. Patients usually undergo surgery followed by aggressive radio- and chemotherapy with the alkylating agent temozolomide (TMZ). Still, median survival is only 12-15 months after diagnosis. Many human cancers including GBMs demonstrate addiction to MYC transcription factor signaling and can become susceptible to inhibition of MYC downstream genes. JQ1 is an effective inhibitor of BET Bromodomains, a class of epigenetic readers regulating expression of downstream MYC targets. Here, we show that BET inhibition decreases viability of patient-derived GBM cell lines. We propose a distinct expression signature of MYCN-elevated GBM cells that correlates with significant sensitivity to BET inhibition. In tumors showing JQ1 sensitivity, we found enrichment of pathways regulating cell cycle, DNA damage response and repair. As DNA repair leads to acquired chemoresistance to TMZ, JQ1 treatment in combination with TMZ synergistically inhibited proliferation of MYCN-elevated cells. Bioinformatic analyses further showed that the expression of MYCN correlates with Aurora Kinase A levels and Aurora Kinase inhibitors indeed showed synergistic efficacy in combination with BET inhibition. Collectively, our data suggest that BET inhibitors could potentiate the efficacy of either TMZ or Aurora Kinase inhibitors in GBM treatment.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Cancer, Matko
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Drews, Lisa F.
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Bengtsson, Johan
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Bolin, Sara, 198 ...
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Rosén, Gabriela
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Westermark, Beng ...
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show more...
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Nelander, Sven
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Forsberg Nilsson ...
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Uhrbom, Lene
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Weishaupt, Holge ...
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Johansson, Fredr ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
- Articles in the publication
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Cell Death and D ...
- By the university
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Uppsala University