Reference Detail

Ref Type Journal Article
PMID (22662154)
Authors Shoji K, Oda K, Kashiyama T, Ikeda Y, Nakagawa S, Sone K, Miyamoto Y, Hiraike H, Tanikawa M, Miyasaka A, Koso T, Matsumoto Y, Wada-Hiraike O, Kawana K, Kuramoto H, McCormick F, Aburatani H, Yano T, Kozuma S, Taketani Y
Title Genotype-dependent efficacy of a dual PI3K/mTOR inhibitor, NVP-BEZ235, and an mTOR inhibitor, RAD001, in endometrial carcinomas.
Journal PloS one
Vol 7
Issue 5
Date 2012
URL
Abstract Text The PI3K (phosphatidylinositol-3-kinase)/mTOR (mammalian target of rapamycin) pathway is frequently activated in endometrial cancer through various PI3K/AKT-activating genetic alterations. We examined the antitumor effect of NVP-BEZ235--a dual PI3K/mTOR inhibitor--and RAD001--an mTOR inhibitor--in 13 endometrial cancer cell lines, all of which possess one or more alterations in PTEN, PIK3CA, and K-Ras. We also combined these compounds with a MAPK pathway inhibitor (PD98059 or UO126) in cell lines with K-Ras alterations (mutations or amplification). PTEN mutant cell lines without K-Ras alterations (n = 9) were more sensitive to both RAD001 and NVP-BEZ235 than were cell lines with K-Ras alterations (n = 4). Dose-dependent growth suppression was more drastically induced by NVP-BEZ235 than by RAD001 in the sensitive cell lines. G1 arrest was induced by NVP-BEZ235 in a dose-dependent manner. We observed in vivo antitumor activity of both RAD001 and NVP-BEZ235 in nude mice. The presence of a MEK inhibitor, PD98059 or UO126, sensitized the K-Ras mutant cells to NVP-BEZ235. Robust growth suppression by NVP-BEZ235 suggests that a dual PI3K/mTOR inhibitor is a promising therapeutic for endometrial carcinomas. Our data suggest that mutational statuses of PTEN and K-Ras might be useful predictors of sensitivity to NVP-BEZ235 in certain endometrial carcinomas.

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Molecular Profile Treatment Approach
PTEN D116fs PI3K Inhibitor (Pan)
PTEN K13* PI3K Inhibitor (Pan)
PTEN K13Q PI3K Inhibitor (Pan)
PTEN E242fs PI3K Inhibitor (Pan)
PTEN E157G PI3K Inhibitor (Pan)
PTEN R55fs PI3K Inhibitor (Pan)
PTEN G165E PI3K Inhibitor (Pan)
PTEN L318fs PI3K Inhibitor (Pan)
PTEN L23F PI3K Inhibitor (Pan)
PTEN K163fs PI3K Inhibitor (Pan)
PTEN S59* PI3K Inhibitor (Pan)
PTEN D92H PI3K Inhibitor (Pan)
PTEN H118fs PI3K Inhibitor (Pan)
PTEN Y336* PI3K Inhibitor (Pan)
PTEN Y176* PI3K Inhibitor (Pan)
PTEN R15I PI3K Inhibitor (Pan)
PTEN V290* PI3K Inhibitor (Pan)
PTEN D326N PI3K Inhibitor (Pan)
PTEN C124fs PI3K Inhibitor (Pan)
PTEN G44D PI3K Inhibitor (Pan)
PTEN M199del PI3K Inhibitor (Pan)
PTEN H93Y PI3K Inhibitor (Pan)
PTEN K263* PI3K Inhibitor (Pan)
PTEN Y68H PI3K Inhibitor (Pan)
PTEN G129R PI3K Inhibitor (Pan)
PTEN H123Q PI3K Inhibitor (Pan)
PTEN S170R PI3K Inhibitor (Pan)
PTEN D107Y PI3K Inhibitor (Pan)
PTEN R173C PI3K Inhibitor (Pan)
PTEN G165V PI3K Inhibitor (Pan)
PTEN K289Nfs*8 PI3K Inhibitor (Pan)
PTEN S302Afs*5 PI3K Inhibitor (Pan)
PTEN R130G PI3K Inhibitor (Pan)
PTEN V54fs PI3K Inhibitor (Pan)
PTEN R335L PI3K Inhibitor (Pan)
PTEN R130K PI3K Inhibitor (Pan)
PTEN Q298fs PI3K Inhibitor (Pan)
PTEN Y65C PI3K Inhibitor (Pan)
PTEN G129V PI3K Inhibitor (Pan)
PTEN L57fs PI3K Inhibitor (Pan)
PTEN Q171* PI3K Inhibitor (Pan)
PTEN V343E PI3K Inhibitor (Pan)
PTEN R173fs PI3K Inhibitor (Pan)
PTEN P96Q PI3K Inhibitor (Pan)
PTEN S170N PI3K Inhibitor (Pan)
PTEN K260fs PI3K Inhibitor (Pan)
PTEN R14fs PI3K Inhibitor (Pan)
PTEN G36R PI3K Inhibitor (Pan)
PTEN A126D PI3K Inhibitor (Pan)
PTEN N323fs PI3K Inhibitor (Pan)
PTEN T321fs PI3K Inhibitor (Pan)
PTEN P95L PI3K Inhibitor (Pan)
PTEN F337fs PI3K Inhibitor (Pan)
PTEN G165* PI3K Inhibitor (Pan)
PTEN G251D PI3K Inhibitor (Pan)
PTEN L247Sfs*6 PI3K Inhibitor (Pan)
PTEN L345Q PI3K Inhibitor (Pan)
PTEN R130P PI3K Inhibitor (Pan)
PTEN L57W PI3K Inhibitor (Pan)
PTEN R233* PI3K Inhibitor (Pan)
PTEN T319del PI3K Inhibitor (Pan)
PTEN E235* PI3K Inhibitor (Pan)
PTEN E201* PI3K Inhibitor (Pan)
PTEN N48K PI3K Inhibitor (Pan)
PTEN C136Y PI3K Inhibitor (Pan)
PTEN E256* PI3K Inhibitor (Pan)
PTEN I122S PI3K Inhibitor (Pan)
PTEN Q245* PI3K Inhibitor (Pan)
PTEN L325F PI3K Inhibitor (Pan)
PTEN E242* PI3K Inhibitor (Pan)
PTEN H93Q PI3K Inhibitor (Pan)
PTEN E284* PI3K Inhibitor (Pan)
PTEN W274fs PI3K Inhibitor (Pan)
PTEN R161G PI3K Inhibitor (Pan)
PTEN D24Y PI3K Inhibitor (Pan)
PTEN F241S PI3K Inhibitor (Pan)
PTEN Q261* PI3K Inhibitor (Pan)
PTEN A126V PI3K Inhibitor (Pan)
PTEN C105F PI3K Inhibitor (Pan)
PTEN A126fs PI3K Inhibitor (Pan)
PTEN D24G PI3K Inhibitor (Pan)
PTEN L108R PI3K Inhibitor (Pan)
PTEN loss PI3K Inhibitor (Pan)
PTEN N63fs PI3K Inhibitor (Pan)
PTEN V119fs PI3K Inhibitor (Pan)
PTEN R130* PI3K Inhibitor (Pan)
PTEN T167A PI3K Inhibitor (Pan)
PTEN L325R PI3K Inhibitor (Pan)
PTEN A121E PI3K Inhibitor (Pan)
PTEN K267fs PI3K Inhibitor (Pan)
PTEN Q214* PI3K Inhibitor (Pan)
PTEN L181P PI3K Inhibitor (Pan)
PTEN Q219* PI3K Inhibitor (Pan)
PTEN Y68fs PI3K Inhibitor (Pan)
PTEN A34D PI3K Inhibitor (Pan)
PTEN D92V PI3K Inhibitor (Pan)
PTEN K260* PI3K Inhibitor (Pan)
PTEN T131I PI3K Inhibitor (Pan)
PTEN H118P PI3K Inhibitor (Pan)
PTEN S294fs PI3K Inhibitor (Pan)
PTEN K62R PI3K Inhibitor (Pan)
PTEN G165R PI3K Inhibitor (Pan)
PTEN L247_P248del PI3K Inhibitor (Pan)
PTEN C136R PI3K Inhibitor (Pan)
PTEN negative PI3K Inhibitor (Pan)
PTEN C71Y PI3K Inhibitor (Pan)
PTEN W111* PI3K Inhibitor (Pan)
PTEN G127N PI3K Inhibitor (Pan)
PTEN C124N PI3K Inhibitor (Pan)
PTEN G251V PI3K Inhibitor (Pan)
PTEN K237fs PI3K Inhibitor (Pan)
PTEN L70fs PI3K Inhibitor (Pan)
PTEN K125* PI3K Inhibitor (Pan)
PTEN E284fs PI3K Inhibitor (Pan)
PTEN D331Tfs*13 PI3K Inhibitor (Pan)
PTEN V343L PI3K Inhibitor (Pan)
PTEN E291* PI3K Inhibitor (Pan)
PTEN Y174N PI3K Inhibitor (Pan)
PTEN G20E PI3K Inhibitor (Pan)
PTEN G127R PI3K Inhibitor (Pan)
PTEN V166Sfs*14 PI3K Inhibitor (Pan)
PTEN P95S PI3K Inhibitor (Pan)
PTEN E7* PI3K Inhibitor (Pan)
PTEN C218* PI3K Inhibitor (Pan)
PTEN A126G PI3K Inhibitor (Pan)
PTEN Y68C PI3K Inhibitor (Pan)
PTEN S227F PI3K Inhibitor (Pan)
PTEN H123Y PI3K Inhibitor (Pan)
PTEN R15K PI3K Inhibitor (Pan)
PTEN N12T PI3K Inhibitor (Pan)
PTEN R130fs PI3K Inhibitor (Pan)
PTEN Y155C PI3K Inhibitor (Pan)
PTEN F56fs PI3K Inhibitor (Pan)
PTEN C136F PI3K Inhibitor (Pan)
PTEN C250fs PI3K Inhibitor (Pan)
PTEN S10N PI3K Inhibitor (Pan)
PTEN S287* PI3K Inhibitor (Pan)
PTEN M134L PI3K Inhibitor (Pan)
PTEN R173P PI3K Inhibitor (Pan)
PTEN G132S PI3K Inhibitor (Pan)
PTEN D92G PI3K Inhibitor (Pan)
PTEN G143fs PI3K Inhibitor (Pan)
PTEN Y27fs PI3K Inhibitor (Pan)
PTEN N292fs PI3K Inhibitor (Pan)
PTEN F154L PI3K Inhibitor (Pan)
PTEN E288fs PI3K Inhibitor (Pan)
PTEN L112R PI3K Inhibitor (Pan)
PTEN D331G PI3K Inhibitor (Pan)
PTEN T167P PI3K Inhibitor (Pan)
PTEN R130L PI3K Inhibitor (Pan)
PTEN K128T PI3K Inhibitor (Pan)
PTEN H93D PI3K Inhibitor (Pan)
PTEN M35R PI3K Inhibitor (Pan)
PTEN V290fs PI3K Inhibitor (Pan)
PTEN C124R PI3K Inhibitor (Pan)
PTEN K128_R130del PI3K Inhibitor (Pan)
PTEN L193fs PI3K Inhibitor (Pan)
PTEN E288* PI3K Inhibitor (Pan)
PTEN G129E PI3K Inhibitor (Pan)
PTEN R15S PI3K Inhibitor (Pan)
PTEN K128Q PI3K Inhibitor (Pan)
PTEN L265fs PI3K Inhibitor (Pan)
PTEN N212Kfs*10 PI3K Inhibitor (Pan)
PTEN T319fs PI3K Inhibitor (Pan)
PTEN A121P PI3K Inhibitor (Pan)
PTEN K254fs PI3K Inhibitor (Pan)
PTEN V158fs PI3K Inhibitor (Pan)
PTEN G127E PI3K Inhibitor (Pan)
PTEN K125L PI3K Inhibitor (Pan)
PTEN C124G PI3K Inhibitor (Pan)
PTEN L42R PI3K Inhibitor (Pan)
PTEN del PI3K Inhibitor (Pan)
PTEN R130A PI3K Inhibitor (Pan)
PTEN N94I PI3K Inhibitor (Pan)
PTEN Y76fs PI3K Inhibitor (Pan)
PTEN A72fs PI3K Inhibitor (Pan)
PTEN D24N PI3K Inhibitor (Pan)
PTEN V275* PI3K Inhibitor (Pan)
PTEN inact mut PI3K Inhibitor (Pan)
PTEN V217D PI3K Inhibitor (Pan)
PTEN E299* PI3K Inhibitor (Pan)
PTEN Y155fs PI3K Inhibitor (Pan)
PTEN L108P PI3K Inhibitor (Pan)
PTEN G129* PI3K Inhibitor (Pan)
PTEN G293fs PI3K Inhibitor (Pan)
PTEN K254Rfs*42 PI3K Inhibitor (Pan)
PTEN N329fs PI3K Inhibitor (Pan)
PTEN N340fs PI3K Inhibitor (Pan)
PTEN P248fs PI3K Inhibitor (Pan)
PTEN T131fs PI3K Inhibitor (Pan)
PTEN L182fs PI3K Inhibitor (Pan)
PTEN G251C PI3K Inhibitor (Pan)
PTEN D331fs PI3K Inhibitor (Pan)
PTEN I122L PI3K Inhibitor (Pan)
PTEN H61R PI3K Inhibitor (Pan)
PTEN H61D PI3K Inhibitor (Pan)
PTEN Y27S PI3K Inhibitor (Pan)
PTEN R130Q PI3K Inhibitor (Pan)
PTEN K289E PI3K Inhibitor (Pan)
PTEN F21A PI3K Inhibitor (Pan)
PTEN Q110* PI3K Inhibitor (Pan)
PTEN T131L PI3K Inhibitor (Pan)
PTEN R335* PI3K Inhibitor (Pan)
PTEN L112P PI3K Inhibitor (Pan)
PTEN K125N PI3K Inhibitor (Pan)
PTEN F341V PI3K Inhibitor (Pan)
PTEN Y68D PI3K Inhibitor (Pan)
PTEN C124S PI3K Inhibitor (Pan)
PTEN Y86fs PI3K Inhibitor (Pan)
PTEN K13E PI3K Inhibitor (Pan)
PTEN D252Y PI3K Inhibitor (Pan)
PTEN K6fs PI3K Inhibitor (Pan)
PTEN Q17* PI3K Inhibitor (Pan)
PTEN A39P PI3K Inhibitor (Pan)
PTEN A126S PI3K Inhibitor (Pan)
PTEN K66fs PI3K Inhibitor (Pan)
PTEN F347L PI3K Inhibitor (Pan)
PTEN T160I PI3K Inhibitor (Pan)
PTEN D92E PI3K Inhibitor (Pan)
PTEN D252G PI3K Inhibitor (Pan)
PTEN V317fs PI3K Inhibitor (Pan)
PTEN K125M PI3K Inhibitor (Pan)
PTEN K125E PI3K Inhibitor (Pan)
PTEN K102fs PI3K Inhibitor (Pan)
PTEN G129D PI3K Inhibitor (Pan)
PTEN P246fs PI3K Inhibitor (Pan)
PTEN Y27D PI3K Inhibitor (Pan)
PTEN K60fs PI3K Inhibitor (Pan)
PTEN Q298* PI3K Inhibitor (Pan)
PTEN V133I PI3K Inhibitor (Pan)
PTEN D92A PI3K Inhibitor (Pan)
PTEN Y65* PI3K Inhibitor (Pan)
PTEN G127V PI3K Inhibitor (Pan)
PTEN H123D PI3K Inhibitor (Pan)
PTEN Y16fs PI3K Inhibitor (Pan)
PTEN E285* PI3K Inhibitor (Pan)
PTEN I122fs PI3K Inhibitor (Pan)
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PTEN mutant endometrial cancer sensitive BEZ235 Preclinical Actionable In a preclinical study, BEZ235 decreased growth of endometrial cancer cells harboring a PTEN nonsense mutation in culture and in xenograft models (PMID: 22662154). 22662154
PTEN mutant endometrial cancer sensitive Everolimus Preclinical - Cell line xenograft Actionable In a preclinical study, Afinitor (everolimus) inhibited growth of endometrial cancer cells harboring a PTEN nonsense mutation in culture and in xenograft models (PMID: 22662154). 22662154
Unknown unknown endometrial cancer not applicable BEZ235 Preclinical Actionable In a preclinical study, BEZ235 suppressed tumor growth in endometrial xenografts (PMID: 22662154). 22662154