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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
28
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pubmed:dateCreated |
2010-7-14
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pubmed:abstractText |
Aurora kinase B inhibitors induce apoptosis secondary to polyploidization and have entered clinical trials as an emerging class of neocytotoxic chemotherapeutics. We demonstrate here that polyploidization neutralizes Mcl-1 function, rendering cancer cells exquisitely dependent on Bcl-XL/-2. This "addiction" can be exploited therapeutically by combining aurora kinase inhibitors and the orally bioavailable BH3 mimetic, ABT-263, which inhibits Bcl-XL, Bcl-2, and Bcl-w. The combination of ABT-263 with aurora B inhibitors produces a synergistic loss of viability in a range of cell lines of divergent tumor origin and exhibits more sustained tumor growth inhibition in vivo compared with aurora B inhibitor monotherapy. These data demonstrate that Bcl-XL/-2 is necessary to support viability during polyploidization in a variety of tumor models and represents a druggable molecular vulnerability with potential therapeutic utility.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-10873104,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-11326099,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-11410528,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-14981513,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-15694340,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-16885368,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-17097561,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-17115033,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-17173063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-17234790,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-17289999,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-17360485,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-17495131,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-17575233,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-17848966,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-18451170,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-18519752,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-19041751,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-19079141,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-7041539,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-8700536,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20616035-8895663
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1091-6490
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pubmed:author |
pubmed-author:AndersonMark GMG,
pubmed-author:ChenJunJ,
pubmed-author:DonawhoCherrie KCK,
pubmed-author:FesikStephen WSW,
pubmed-author:GlaserKeith BKB,
pubmed-author:HuangXiaoliX,
pubmed-author:LiJunlingJ,
pubmed-author:LiLeimingL,
pubmed-author:LinXiaoyuX,
pubmed-author:McLoughlinShaunS,
pubmed-author:PalmaJoannJ,
pubmed-author:RodriguezLuis ELE,
pubmed-author:ShahO JameelOJ,
pubmed-author:ShenYuY,
pubmed-author:TangHuaH,
pubmed-author:WarderScott ESE
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pubmed:issnType |
Electronic
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pubmed:day |
13
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pubmed:volume |
107
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12634-9
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pubmed:dateRevised |
2011-7-11
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pubmed:meshHeading |
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pubmed:year |
2010
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pubmed:articleTitle |
Bcl-XL represents a druggable molecular vulnerability during aurora B inhibitor-mediated polyploidization.
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pubmed:affiliation |
Oncology Division and Advanced Technologies, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6121, USA.
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pubmed:publicationType |
Journal Article
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