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Ref Type Journal Article
PMID (25544636)
Authors Schwartz S, Wongvipat J, Trigwell CB, Hancox U, Carver BS, Rodrik-Outmezguine V, Will M, Yellen P, de Stanchina E, Baselga J, Scher HI, Barry ST, Sawyers CL, Chandarlapaty S, Rosen N
Title Feedback suppression of PI3Kα signaling in PTEN-mutated tumors is relieved by selective inhibition of PI3Kβ.
Journal Cancer cell
Vol 27
Issue 1
Date 2015 Jan 12
URL
Abstract Text In PTEN-mutated tumors, we show that PI3Kα activity is suppressed and PI3K signaling is driven by PI3Kβ. A selective inhibitor of PI3Kβ inhibits the Akt/mTOR pathway in these tumors but not in those driven by receptor tyrosine kinases. However, inhibition of PI3Kβ only transiently inhibits Akt/mTOR signaling because it relieves feedback inhibition of IGF1R and other receptors and thus causes activation of PI3Kα and a rebound in downstream signaling. This rebound is suppressed and tumor growth inhibition enhanced with combined inhibition of PI3Kα and PI3Kβ. In PTEN-deficient models of prostate cancer, this effective inhibition of PI3K causes marked activation of androgen receptor activity. Combined inhibition of both PI3K isoforms and androgen receptor results in major tumor regressions.

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Molecular Profile Treatment Approach
PTEN R335L PIK3CB inhibitor
PTEN D107Y PIK3CB inhibitor
PTEN L325F PIK3CB inhibitor
PTEN Y65* PIK3CB inhibitor
PTEN D24Y PIK3CB inhibitor
PTEN V119del PIK3CB inhibitor
PTEN Y315* PIK3CB inhibitor
PTEN L247Sfs*6 PIK3CB inhibitor
PTEN R74Dfs*25 PIK3CB inhibitor
PTEN H123D PIK3CB inhibitor
PTEN N48S PIK3CB inhibitor
PTEN I122fs PIK3CB inhibitor
PTEN R335* PIK3CB inhibitor
PTEN C124W PIK3CB inhibitor
PTEN E18* PIK3CB inhibitor
PTEN G36R PIK3CB inhibitor
PTEN Y68H PIK3CB inhibitor
PTEN R142P PIK3CB inhibitor
PTEN V217G PIK3CB inhibitor
PTEN D77* PIK3CB inhibitor
PTEN A121E PIK3CB inhibitor
PTEN K342* PIK3CB inhibitor
PTEN D268Gfs*30 PIK3CB inhibitor
PTEN H93Y PIK3CB inhibitor
PTEN R173C PIK3CB inhibitor
PTEN E91* PIK3CB inhibitor
PTEN V166Sfs*14 PIK3CB inhibitor
PTEN Y155fs PIK3CB inhibitor
PTEN H123R PIK3CB inhibitor
PTEN G129* PIK3CB inhibitor
PTEN A126P PIK3CB inhibitor
PTEN D22E PIK3CB inhibitor
PTEN Y174N PIK3CB inhibitor
PTEN R159S PIK3CB inhibitor
PTEN N276T PIK3CB inhibitor
PTEN L182P PIK3CB inhibitor
PTEN I33del PIK3CB inhibitor
PTEN Q261* PIK3CB inhibitor
PTEN Y27S PIK3CB inhibitor
PTEN K62R PIK3CB inhibitor
PTEN V317fs PIK3CB inhibitor
PTEN L108P PIK3CB inhibitor
PTEN D116fs PIK3CB inhibitor
PTEN C136R PIK3CB inhibitor
PTEN D24N PIK3CB inhibitor
PTEN D331fs PIK3CB inhibitor
PTEN V53E PIK3CB inhibitor
PTEN P95L PIK3CB inhibitor
PTEN D252Y PIK3CB inhibitor
PTEN N323fs PIK3CB inhibitor
PTEN A72fs PIK3CB inhibitor
PTEN S302Afs*5 PIK3CB inhibitor
PTEN G165R PIK3CB inhibitor
PTEN L112P PIK3CB inhibitor
PTEN C83* PIK3CB inhibitor
PTEN C250fs PIK3CB inhibitor
PTEN G36* PIK3CB inhibitor
PTEN E307* PIK3CB inhibitor
PTEN Y176* PIK3CB inhibitor
PTEN M35R PIK3CB inhibitor
PTEN G165E PIK3CB inhibitor
PTEN P96del PIK3CB inhibitor
PTEN P96Q PIK3CB inhibitor
PTEN G132V PIK3CB inhibitor
PTEN P38R PIK3CB inhibitor
PTEN N48I PIK3CB inhibitor
PTEN T319fs PIK3CB inhibitor
PTEN S170N PIK3CB inhibitor
PTEN D326H PIK3CB inhibitor
PTEN A126fs PIK3CB inhibitor
PTEN I101F PIK3CB inhibitor
PTEN C71W PIK3CB inhibitor
PTEN V255A PIK3CB inhibitor
PTEN K6* PIK3CB inhibitor
PTEN Y188del PIK3CB inhibitor
PTEN F56S PIK3CB inhibitor
PTEN K6E PIK3CB inhibitor
PTEN Q17del PIK3CB inhibitor
PTEN P246fs PIK3CB inhibitor
PTEN C105W PIK3CB inhibitor
PTEN K128_R130del PIK3CB inhibitor
PTEN V217D PIK3CB inhibitor
PTEN C124G PIK3CB inhibitor
PTEN A126V PIK3CB inhibitor
PTEN T321fs PIK3CB inhibitor
PTEN Y76fs PIK3CB inhibitor
PTEN L70P PIK3CB inhibitor
PTEN R41* PIK3CB inhibitor
PTEN T167A PIK3CB inhibitor
PTEN G129E PIK3CB inhibitor
PTEN T382S PIK3CB inhibitor
PTEN L70R PIK3CB inhibitor
PTEN C218* PIK3CB inhibitor
PTEN G129V PIK3CB inhibitor
PTEN D92A PIK3CB inhibitor
PTEN H61L PIK3CB inhibitor
PTEN T160del PIK3CB inhibitor
PTEN V158fs PIK3CB inhibitor
PTEN K6fs PIK3CB inhibitor
PTEN S287* PIK3CB inhibitor
PTEN V290fs PIK3CB inhibitor
PTEN K125* PIK3CB inhibitor
PTEN E99* PIK3CB inhibitor
PTEN R14fs PIK3CB inhibitor
PTEN Y336* PIK3CB inhibitor
PTEN E242fs PIK3CB inhibitor
PTEN C105F PIK3CB inhibitor
PTEN Y68N PIK3CB inhibitor
PTEN K13* PIK3CB inhibitor
PTEN E106* PIK3CB inhibitor
PTEN Y88* PIK3CB inhibitor
PTEN M134R PIK3CB inhibitor
PTEN H61D PIK3CB inhibitor
PTEN del PIK3CB inhibitor
PTEN P38T PIK3CB inhibitor
PTEN N292fs PIK3CB inhibitor
PTEN M264R PIK3CB inhibitor
PTEN C211* PIK3CB inhibitor
PTEN H61P PIK3CB inhibitor
PTEN D24del PIK3CB inhibitor
PTEN P95R PIK3CB inhibitor
PTEN L140* PIK3CB inhibitor
PTEN S10N PIK3CB inhibitor
PTEN D324del PIK3CB inhibitor
PTEN M35V PIK3CB inhibitor
PTEN S170I PIK3CB inhibitor
PTEN Y177* PIK3CB inhibitor
PTEN K221* PIK3CB inhibitor
PTEN Y155N PIK3CB inhibitor
PTEN G127E PIK3CB inhibitor
PTEN A121P PIK3CB inhibitor
PTEN M134T PIK3CB inhibitor
PTEN G132D PIK3CB inhibitor
PTEN C71Y PIK3CB inhibitor
PTEN V175E PIK3CB inhibitor
PTEN C124N PIK3CB inhibitor
PTEN Y65C PIK3CB inhibitor
PTEN E73K PIK3CB inhibitor
PTEN Y27C PIK3CB inhibitor
PTEN R130P PIK3CB inhibitor
PTEN E285* PIK3CB inhibitor
PTEN S10del PIK3CB inhibitor
PTEN K260fs PIK3CB inhibitor
PTEN F56C PIK3CB inhibitor
PTEN T319* PIK3CB inhibitor
PTEN I253* PIK3CB inhibitor
PTEN Q245* PIK3CB inhibitor
PTEN F145* PIK3CB inhibitor
PTEN K163* PIK3CB inhibitor
PTEN G156V PIK3CB inhibitor
PTEN K266* PIK3CB inhibitor
PTEN M134L PIK3CB inhibitor
PTEN inact mut PIK3CB inhibitor
PTEN R15K PIK3CB inhibitor
PTEN T167N PIK3CB inhibitor
PTEN W111R PIK3CB inhibitor
PTEN Q298fs PIK3CB inhibitor
PTEN Y176del PIK3CB inhibitor
PTEN D107V PIK3CB inhibitor
PTEN Q171E PIK3CB inhibitor
PTEN T319del PIK3CB inhibitor
PTEN K322E PIK3CB inhibitor
PTEN Y138L PIK3CB inhibitor
PTEN L70V PIK3CB inhibitor
PTEN K289Nfs*8 PIK3CB inhibitor
PTEN G165V PIK3CB inhibitor
PTEN D24V PIK3CB inhibitor
PTEN T131I PIK3CB inhibitor
PTEN Q17* PIK3CB inhibitor
PTEN E114* PIK3CB inhibitor
PTEN N12T PIK3CB inhibitor
PTEN L139* PIK3CB inhibitor
PTEN Y68D PIK3CB inhibitor
PTEN K147* PIK3CB inhibitor
PTEN G127N PIK3CB inhibitor
PTEN L23S PIK3CB inhibitor
PTEN Q149* PIK3CB inhibitor
PTEN N323Kfs*2 PIK3CB inhibitor
PTEN R130* PIK3CB inhibitor
PTEN Y16fs PIK3CB inhibitor
PTEN C124S PIK3CB inhibitor
PTEN T277del PIK3CB inhibitor
PTEN N276S PIK3CB inhibitor
PTEN Y46* PIK3CB inhibitor
PTEN D109fs PIK3CB inhibitor
PTEN L247_P248del PIK3CB inhibitor
PTEN Y225* PIK3CB inhibitor
PTEN S10I PIK3CB inhibitor
PTEN P95S PIK3CB inhibitor
PTEN D92Y PIK3CB inhibitor
PTEN G129D PIK3CB inhibitor
PTEN T348I PIK3CB inhibitor
PTEN P38H PIK3CB inhibitor
PTEN G156W PIK3CB inhibitor
PTEN G293* PIK3CB inhibitor
PTEN R173P PIK3CB inhibitor
PTEN M134I PIK3CB inhibitor
PTEN L57fs PIK3CB inhibitor
PTEN T131A PIK3CB inhibitor
PTEN G251C PIK3CB inhibitor
PTEN D326Y PIK3CB inhibitor
PTEN M205I PIK3CB inhibitor
PTEN K125E PIK3CB inhibitor
PTEN L265fs PIK3CB inhibitor
PTEN F271S PIK3CB inhibitor
PTEN R173H PIK3CB inhibitor
PTEN V275G PIK3CB inhibitor
PTEN K66fs PIK3CB inhibitor
PTEN D92V PIK3CB inhibitor
PTEN V45del PIK3CB inhibitor
PTEN Y27D PIK3CB inhibitor
PTEN R130S PIK3CB inhibitor
PTEN Y174* PIK3CB inhibitor
PTEN T277N PIK3CB inhibitor
PTEN T131fs PIK3CB inhibitor
PTEN Q110* PIK3CB inhibitor
PTEN S227F PIK3CB inhibitor
PTEN A126D PIK3CB inhibitor
PTEN L193P PIK3CB inhibitor
PTEN I122N PIK3CB inhibitor
PTEN Y178del PIK3CB inhibitor
PTEN L108R PIK3CB inhibitor
PTEN F90S PIK3CB inhibitor
PTEN V54del PIK3CB inhibitor
PTEN F21A PIK3CB inhibitor
PTEN W111G PIK3CB inhibitor
PTEN K330* PIK3CB inhibitor
PTEN G44D PIK3CB inhibitor
PTEN K267fs PIK3CB inhibitor
PTEN C124F PIK3CB inhibitor
PTEN V133I PIK3CB inhibitor
PTEN L247* PIK3CB inhibitor
PTEN F337fs PIK3CB inhibitor
PTEN L23V PIK3CB inhibitor
PTEN L146* PIK3CB inhibitor
PTEN H61R PIK3CB inhibitor
PTEN F257L PIK3CB inhibitor
PTEN D52del PIK3CB inhibitor
PTEN V166E PIK3CB inhibitor
PTEN R142W PIK3CB inhibitor
PTEN R234* PIK3CB inhibitor
PTEN K269* PIK3CB inhibitor
PTEN M35K PIK3CB inhibitor
PTEN S59P PIK3CB inhibitor
PTEN G127R PIK3CB inhibitor
PTEN V119G PIK3CB inhibitor
PTEN L325R PIK3CB inhibitor
PTEN Y27fs PIK3CB inhibitor
PTEN D107G PIK3CB inhibitor
PTEN H93D PIK3CB inhibitor
PTEN Q87* PIK3CB inhibitor
PTEN V290Sfs*8 PIK3CB inhibitor
PTEN K183Ifs*15 PIK3CB inhibitor
PTEN F341V PIK3CB inhibitor
PTEN Y46H PIK3CB inhibitor
PTEN L345Q PIK3CB inhibitor
PTEN L152P PIK3CB inhibitor
PTEN K6del PIK3CB inhibitor
PTEN V249E PIK3CB inhibitor
PTEN E284fs PIK3CB inhibitor
PTEN A126G PIK3CB inhibitor
PTEN H123Y PIK3CB inhibitor
PTEN K13Q PIK3CB inhibitor
PTEN Q171P PIK3CB inhibitor
PTEN H123L PIK3CB inhibitor
PTEN K125M PIK3CB inhibitor
PTEN C136Y PIK3CB inhibitor
PTEN Q171R PIK3CB inhibitor
PTEN N340fs PIK3CB inhibitor
PTEN E242* PIK3CB inhibitor
PTEN S170R PIK3CB inhibitor
PTEN I135K PIK3CB inhibitor
PTEN K197* PIK3CB inhibitor
PTEN D24H PIK3CB inhibitor
PTEN T232A PIK3CB inhibitor
PTEN K254Rfs*42 PIK3CB inhibitor
PTEN E150* PIK3CB inhibitor
PTEN Y188* PIK3CB inhibitor
PTEN Q17Kfs*7 PIK3CB inhibitor
PTEN P248fs PIK3CB inhibitor
PTEN I33N PIK3CB inhibitor
PTEN T131N PIK3CB inhibitor
PTEN Y177C PIK3CB inhibitor
PTEN W111S PIK3CB inhibitor
PTEN K237fs PIK3CB inhibitor
PTEN L152R PIK3CB inhibitor
PTEN A39P PIK3CB inhibitor
PTEN Y68C PIK3CB inhibitor
PTEN R55fs PIK3CB inhibitor
PTEN Y27N PIK3CB inhibitor
PTEN E256* PIK3CB inhibitor
PTEN D109* PIK3CB inhibitor
PTEN H141P PIK3CB inhibitor
PTEN W274* PIK3CB inhibitor
PTEN Y174D PIK3CB inhibitor
PTEN L182fs PIK3CB inhibitor
PTEN I101T PIK3CB inhibitor
PTEN M198R PIK3CB inhibitor
PTEN Q298* PIK3CB inhibitor
PTEN Y65S PIK3CB inhibitor
PTEN L57S PIK3CB inhibitor
PTEN K13E PIK3CB inhibitor
PTEN L140F PIK3CB inhibitor
PTEN A151P PIK3CB inhibitor
PTEN Q245P PIK3CB inhibitor
PTEN I28N PIK3CB inhibitor
PTEN E43* PIK3CB inhibitor
PTEN R130fs PIK3CB inhibitor
PTEN C105Y PIK3CB inhibitor
PTEN N184Efs*16 PIK3CB inhibitor
PTEN G129R PIK3CB inhibitor
PTEN D326* PIK3CB inhibitor
PTEN G251D PIK3CB inhibitor
PTEN R15I PIK3CB inhibitor
PTEN C136F PIK3CB inhibitor
PTEN T160I PIK3CB inhibitor
PTEN L42R PIK3CB inhibitor
PTEN negative PIK3CB inhibitor
PTEN G132del PIK3CB inhibitor
PTEN I8Dfs*3 PIK3CB inhibitor
PTEN Q171* PIK3CB inhibitor
PTEN M199del PIK3CB inhibitor
PTEN G127* PIK3CB inhibitor
PTEN D92H PIK3CB inhibitor
PTEN L23F PIK3CB inhibitor
PTEN Y240* PIK3CB inhibitor
PTEN P96R PIK3CB inhibitor
PTEN T131L PIK3CB inhibitor
PTEN L57W PIK3CB inhibitor
PTEN V343E PIK3CB inhibitor
PTEN Q214* PIK3CB inhibitor
PTEN R173fs PIK3CB inhibitor
PTEN S294fs PIK3CB inhibitor
PTEN E288fs PIK3CB inhibitor
PTEN D252G PIK3CB inhibitor
PTEN I101S PIK3CB inhibitor
PTEN N212Kfs*10 PIK3CB inhibitor
PTEN G143fs PIK3CB inhibitor
PTEN K263* PIK3CB inhibitor
PTEN K102fs PIK3CB inhibitor
PTEN Y177S PIK3CB inhibitor
PTEN N63fs PIK3CB inhibitor
PTEN H118fs PIK3CB inhibitor
PTEN K260* PIK3CB inhibitor
PTEN K125N PIK3CB inhibitor
PTEN C211W PIK3CB inhibitor
PTEN P38F PIK3CB inhibitor
PTEN H61K PIK3CB inhibitor
PTEN F241S PIK3CB inhibitor
PTEN R130G PIK3CB inhibitor
PTEN R233* PIK3CB inhibitor
PTEN R130A PIK3CB inhibitor
PTEN E157G PIK3CB inhibitor
PTEN V54fs PIK3CB inhibitor
PTEN H123Q PIK3CB inhibitor
PTEN R15S PIK3CB inhibitor
PTEN G36E PIK3CB inhibitor
PTEN K125L PIK3CB inhibitor
PTEN W111fs PIK3CB inhibitor
PTEN R14G PIK3CB inhibitor
PTEN C124L PIK3CB inhibitor
PTEN K254fs PIK3CB inhibitor
PTEN L193fs PIK3CB inhibitor
PTEN H272P PIK3CB inhibitor
PTEN K163fs PIK3CB inhibitor
PTEN A34D PIK3CB inhibitor
PTEN I253N PIK3CB inhibitor
PTEN N276A PIK3CB inhibitor
PTEN R159I PIK3CB inhibitor
PTEN H93Q PIK3CB inhibitor
PTEN H93L PIK3CB inhibitor
PTEN L42P PIK3CB inhibitor
PTEN N94I PIK3CB inhibitor
PTEN C124R PIK3CB inhibitor
PTEN L112R PIK3CB inhibitor
PTEN T131P PIK3CB inhibitor
PTEN Y88D PIK3CB inhibitor
PTEN M264T PIK3CB inhibitor
PTEN L318fs PIK3CB inhibitor
PTEN R130K PIK3CB inhibitor
PTEN V275* PIK3CB inhibitor
PTEN K60fs PIK3CB inhibitor
PTEN I135R PIK3CB inhibitor
PTEN S59* PIK3CB inhibitor
PTEN G282* PIK3CB inhibitor
PTEN W274fs PIK3CB inhibitor
PTEN N329fs PIK3CB inhibitor
PTEN P38L PIK3CB inhibitor
PTEN Y155C PIK3CB inhibitor
PTEN L181P PIK3CB inhibitor
PTEN V166G PIK3CB inhibitor
PTEN V290* PIK3CB inhibitor
PTEN E284* PIK3CB inhibitor
PTEN L320S PIK3CB inhibitor
PTEN Y155H PIK3CB inhibitor
PTEN D331Tfs*13 PIK3CB inhibitor
PTEN E314* PIK3CB inhibitor
PTEN G132S PIK3CB inhibitor
PTEN T167P PIK3CB inhibitor
PTEN W111* PIK3CB inhibitor
PTEN G165* PIK3CB inhibitor
PTEN E291Gfs*7 PIK3CB inhibitor
PTEN L57* PIK3CB inhibitor
PTEN N48K PIK3CB inhibitor
PTEN R189* PIK3CB inhibitor
PTEN E288* PIK3CB inhibitor
PTEN S229* PIK3CB inhibitor
PTEN F347L PIK3CB inhibitor
PTEN G132C PIK3CB inhibitor
PTEN E7* PIK3CB inhibitor
PTEN L70fs PIK3CB inhibitor
PTEN E235* PIK3CB inhibitor
PTEN K267* PIK3CB inhibitor
PTEN T321* PIK3CB inhibitor
PTEN P339L PIK3CB inhibitor
PTEN G293fs PIK3CB inhibitor
PTEN K128Q PIK3CB inhibitor
PTEN K6I PIK3CB inhibitor
PTEN F56fs PIK3CB inhibitor
PTEN E157* PIK3CB inhibitor
PTEN A126S PIK3CB inhibitor
PTEN I122L PIK3CB inhibitor
PTEN C105G PIK3CB inhibitor
PTEN Y178* PIK3CB inhibitor
PTEN D162Y PIK3CB inhibitor
PTEN D326N PIK3CB inhibitor
PTEN R161G PIK3CB inhibitor
PTEN D24G PIK3CB inhibitor
PTEN I33S PIK3CB inhibitor
PTEN I122F PIK3CB inhibitor
PTEN R130L PIK3CB inhibitor
PTEN D92E PIK3CB inhibitor
PTEN G20E PIK3CB inhibitor
PTEN I67K PIK3CB inhibitor
PTEN G251V PIK3CB inhibitor
PTEN D252V PIK3CB inhibitor
PTEN E299* PIK3CB inhibitor
PTEN I122S PIK3CB inhibitor
PTEN D162del PIK3CB inhibitor
PTEN Y16D PIK3CB inhibitor
PTEN L108H PIK3CB inhibitor
PTEN H118P PIK3CB inhibitor
PTEN R130Q PIK3CB inhibitor
PTEN M198K PIK3CB inhibitor
PTEN M134del PIK3CB inhibitor
PTEN I101N PIK3CB inhibitor
PTEN A34P PIK3CB inhibitor
PTEN K254* PIK3CB inhibitor
PTEN P95Q PIK3CB inhibitor
PTEN D92G PIK3CB inhibitor
PTEN V217fs PIK3CB inhibitor
PTEN K128E PIK3CB inhibitor
PTEN E201* PIK3CB inhibitor
PTEN Y177D PIK3CB inhibitor
PTEN R159L PIK3CB inhibitor
PTEN V119fs PIK3CB inhibitor
PTEN Y46D PIK3CB inhibitor
PTEN R159F PIK3CB inhibitor
PTEN K128T PIK3CB inhibitor
PTEN G230* PIK3CB inhibitor
PTEN Q171K PIK3CB inhibitor
PTEN S385* PIK3CB inhibitor
PTEN E291* PIK3CB inhibitor
PTEN Y76* PIK3CB inhibitor
PTEN Y65D PIK3CB inhibitor
PTEN Y68fs PIK3CB inhibitor
PTEN Q219* PIK3CB inhibitor
PTEN C124fs PIK3CB inhibitor
PTEN C136W PIK3CB inhibitor
PTEN N276K PIK3CB inhibitor
PTEN N117S PIK3CB inhibitor
PTEN F154L PIK3CB inhibitor
PTEN H93P PIK3CB inhibitor
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
Gene 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 del prostate cancer sensitive AZD8186 + Enzalutamide Preclinical Actionable In a preclinical study, AZD8186 and Xtandi (enzalutamide) combination treatment resulted in suppression of tumor growth in animal models of prostate cancer harboring PTEN gene deletion (PMID: 25544636). 25544636
PTEN del prostate cancer sensitive Alpelisib + AZD8186 Preclinical Actionable In a preclinical study, AZD8186 and Alpelisib (BYL719) combination treatment resulted in minor inhibition of tumor growth in animal models of prostate cancer harboring PTEN gene deletion (PMID: 25544636). 25544636
PTEN del prostate cancer sensitive Alpelisib + AZD8186 + Enzalutamide Preclinical Actionable In a preclinical study, AZD8186, Alpelisib (BYL719), and Xtandi (enzalutamide) combination treatment resulted in near-complete suppression of tumor growth in animal models of prostate cancer harboring PTEN gene deletion (PMID: 25544636). 25544636