Show simple item record

Combination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal cancer

dc.contributor.authorRoper, Jatin
dc.contributor.authorSinnamon, Mark J.
dc.contributor.authorCoffee, Erin M.
dc.contributor.authorBelmont, Peter
dc.contributor.authorKeung, Lily
dc.contributor.authorGeorgeon-Richard, Larissa
dc.contributor.authorWang, Wei Vivian
dc.contributor.authorFaber, Anthony C.
dc.contributor.authorYun, Jihye
dc.contributor.authorBronson, Roderick T.
dc.contributor.authorMartin, Eric S.
dc.contributor.authorTsichlis, Philip N.
dc.contributor.authorHung, Kenneth E.
dc.contributor.authorYilmaz, Omer
dc.date.accessioned2018-07-23T19:03:07Z
dc.date.available2018-07-23T19:03:07Z
dc.date.issued2014-02
dc.date.submitted2014-02
dc.identifier.issn0304-3835
dc.identifier.urihttp://hdl.handle.net/1721.1/117053
dc.description.abstractPI3K inhibition in combination with other agents has not been studied in the context of PIK3CA wild-type, KRAS mutant cancer. In a screen of phospho-kinases, PI3K inhibition of KRAS mutant colorectal cancer cells activated the MAPK pathway. Combination PI3K/MEK inhibition with NVP-BKM120 and PD-0325901 induced tumor regression in a mouse model of PIK3CA wild-type, KRAS mutant colorectal cancer, which was mediated by inhibition of mTORC1, inhibition of MCL-1, and activation of BIM. These findings implicate mitochondrial-dependent apoptotic mechanisms as determinants for the efficacy of PI3K/MEK inhibition in the treatment of PIK3CA wild-type, KRAS mutant cancer. Keywords: PI3K; MEK; KRAS; Colorectal cancer; Mouse model of canceren_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/J.CANLET.2014.02.018en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleCombination PI3K/MEK inhibition promotes tumor apoptosis and regression in PIK3CA wild-type, KRAS mutant colorectal canceren_US
dc.typeArticleen_US
dc.identifier.citationRoper, Jatin et al. “Combination PI3K/MEK Inhibition Promotes Tumor Apoptosis and Regression in PIK3CA Wild-Type, KRAS Mutant Colorectal Cancer.” Cancer Letters 347, 2 (June 2014): 204–211 © 2014 Elsevier Ireland Ltden_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorYilmaz, Omer
dc.relation.journalCancer Lettersen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2018-07-13T16:24:20Z
dspace.orderedauthorsRoper, Jatin; Sinnamon, Mark J.; Coffee, Erin M.; Belmont, Peter; Keung, Lily; Georgeon-Richard, Larissa; Wang, Wei Vivian; Faber, Anthony C.; Yun, Jihye; Yilmaz, Ömer H.; Bronson, Roderick T.; Martin, Eric S.; Tsichlis, Philip N.; Hung, Kenneth E.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-7577-4612
mit.licensePUBLISHER_CCen_US


Files in this item

Thumbnail
Name:
nihms-615364.pdf
Size:
1.304Mb
Format:
PDF
View/Open

This item appears in the following Collection(s)

Show simple item record