{"id":"https://openalex.org/W4361944602","doi":"https://doi.org/10.1158/1078-0432.c.6521319","title":"Data from PIK3CA and AKT1 Mutations Have Distinct Effects on Sensitivity to Targeted Pathway Inhibitors in an Isogenic Luminal Breast Cancer Model System","display_name":"Data from PIK3CA and AKT1 Mutations Have Distinct Effects on Sensitivity to Targeted Pathway Inhibitors in an Isogenic Luminal Breast Cancer Model System","publication_year":2023,"publication_date":"2023-03-31","ids":{"openalex":"https://openalex.org/W4361944602","doi":"https://doi.org/10.1158/1078-0432.c.6521319"},"language":"en","primary_location":{"id":"doi:10.1158/1078-0432.c.6521319","doi":"https://doi.org/10.1158/1078-0432.c.6521319","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/1078-0432.c.6521319","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"volume":null,"type":"other","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"http://dx.doi.org/10.1158/1078-0432.c.6521319","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5004000071","display_name":"Julia A. Beaver","orcid":"https://orcid.org/0000-0002-0725-2863","observed_orcids":["https://orcid.org/0000-0002-0725-2863"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Julia A. Beaver","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5017837459","display_name":"John P. Gustin","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"John P. Gustin","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":null,"display_name":"Kyung H. Yi","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Kyung H. Yi","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5058513374","display_name":"Anandita Rajpurohit","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Anandita Rajpurohit","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5101850908","display_name":"Matthew Thomas","orcid":"https://orcid.org/0009-0001-8029-463X","observed_orcids":["https://orcid.org/0009-0001-8029-463X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Matthew Thomas","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5031985000","display_name":"Samuel F. Gilbert","orcid":"https://orcid.org/0000-0002-0440-1173","observed_orcids":["https://orcid.org/0000-0002-0440-1173","https://orcid.org/0000-0002-6833-6788"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Samuel F. Gilbert","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023210852","display_name":"D. Marc Rosen","orcid":"https://orcid.org/0009-0008-4191-8754","observed_orcids":["https://orcid.org/0009-0008-4191-8754"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"D. Marc Rosen","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5091723009","display_name":"Ben Ho Park","orcid":"https://orcid.org/0000-0001-8119-2291","observed_orcids":["https://orcid.org/0000-0001-8119-2291"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ben Ho Park","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5036452213","display_name":"Josh David Lauring","orcid":"https://orcid.org/0000-0002-4312-704X","observed_orcids":["https://orcid.org/0000-0002-4312-704X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Josh Lauring","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":1.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":1.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12829","display_name":"Advanced Breast Cancer Therapies","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T11339","display_name":"Metabolism, Diabetes, and Cancer","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/pik3ca-e545k-mutation","display_name":"PIK3CA E545K mutation","score":0.8870000243186951},{"id":"https://openalex.org/keywords/akt1-e17k-mutation","display_name":"AKT1 E17K mutation","score":0.9240000247955322},{"id":"https://openalex.org/keywords/pi3k-akt-mtor-pathway","display_name":"PI3K/AKT/mTOR pathway","score":0.9269999861717224},{"id":"https://openalex.org/keywords/luminal-breast-cancer","display_name":"luminal breast cancer","score":0.9409999847412109},{"id":"https://openalex.org/keywords/drug-sensitivity","display_name":"drug sensitivity","score":0.6340000033378601},{"id":"https://openalex.org/keywords/pi3k-inhibitors","display_name":"PI3K inhibitors","score":0.8330000042915344},{"id":"https://openalex.org/keywords/gdc-0941","display_name":"GDC-0941","score":0.9570000171661377},{"id":"https://openalex.org/keywords/mk-2206","display_name":"MK-2206","score":0.9829999804496765},{"id":"https://openalex.org/keywords/akt-inhibitors","display_name":"AKT inhibitors","score":0.734000027179718},{"id":"https://openalex.org/keywords/predictive-biomarkers","display_name":"predictive biomarkers","score":0.8370000123977661},{"id":"https://openalex.org/keywords/mcf-7-cells","display_name":"MCF-7 cells","score":0.8379999995231628},{"id":"https://openalex.org/keywords/oncogenes","display_name":"oncogenes","score":0.5339999794960022},{"id":"https://openalex.org/keywords/tumor-growth","display_name":"tumor growth","score":0.4620000123977661},{"id":"https://openalex.org/keywords/proliferation","display_name":"proliferation","score":0.4560000002384186}],"concepts":[{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.730197012424469},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.6060304045677185},{"id":"https://openalex.org/C154137905","wikidata":"https://www.wikidata.org/wiki/Q17816452","display_name":"AKT1","level":4,"score":0.5862371921539307},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5141165852546692},{"id":"https://openalex.org/C11960822","wikidata":"https://www.wikidata.org/wiki/Q242736","display_name":"Phosphorylation","level":2,"score":0.4793618321418762},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.4697069823741913},{"id":"https://openalex.org/C153911025","wikidata":"https://www.wikidata.org/wiki/Q7202","display_name":"Molecular biology","level":1,"score":0.44970107078552246},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.445444256067276},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.30546239018440247},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.2645052969455719},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.2467697560787201}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1158/1078-0432.c.6521319","doi":"https://doi.org/10.1158/1078-0432.c.6521319","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/1078-0432.c.6521319","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},{"id":"doi:10.1158/1078-0432.c.6521319.v1","doi":"https://doi.org/10.1158/1078-0432.c.6521319.v1","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/1078-0432.c.6521319.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1158/1078-0432.c.6521319","doi":"https://doi.org/10.1158/1078-0432.c.6521319","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/1078-0432.c.6521319","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.98580002784729,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2169128676","https://openalex.org/W2740898850","https://openalex.org/W4245772831","https://openalex.org/W2326341303","https://openalex.org/W4361816137","https://openalex.org/W2139712038","https://openalex.org/W3013587102","https://openalex.org/W4392692178","https://openalex.org/W2086651571","https://openalex.org/W4412642237"],"abstract_inverted_index":{"Abstract":[0],"Purpose:":[1],"Activating":[2],"mutations":[3,30,50,78,209],"in":[4,11,95,108,148,151,172,199],"the":[5,12,43,60,74,80,155,182,187,216,230],"phosphoinositide-3-kinase":[6],"(PI3K)/AKT/mTOR":[7],"pathway":[8,49,166,208,217],"are":[9,19],"present":[10],"majority":[13],"of":[14,23,39,46,62,76,115,121,137,154,232],"breast":[15,67,203],"cancers":[16],"and":[17,26,124,134,150,169,186,221],"therefore":[18],"a":[20,63,195,200],"major":[21],"focus":[22],"drug":[24,52],"development":[25],"clinical":[27],"trials.":[28],"Pathway":[29],"have":[31,227],"been":[32],"proposed":[33],"as":[34],"predictive":[35],"biomarkers":[36],"for":[37,229],"efficacy":[38],"PI3K-targeted":[40],"therapies.":[41,241],"However,":[42],"precise":[44],"contribution":[45],"distinct":[47,223],"PI3K":[48,183,207],"to":[51,72,90,98,181,213,236,239],"sensitivity":[53,180,212],"is":[54,194],"unknown.":[55],"Experimental":[56],"Design:":[57],"We":[58,84],"describe":[59],"creation":[61],"physiologic":[64],"human":[65,201],"luminal":[66,202],"cancer":[68,204],"cell":[69,82,87],"line":[70],"model":[71],"study":[73],"phenotype":[75],"these":[77],"using":[79],"MCF-7":[81,96],"line.":[83],"used":[85],"somatic":[86],"gene":[88],"targeting":[89,215],"\u201ccorrect\u201d":[91],"PIK3CA":[92,117,142,162],"E545K-mutant":[93],"alleles":[94],"cells":[97,144],"wild-type":[99,111,143,163],"sequence.":[100],"The":[101],"AKT1":[102,156,177],"E17K":[103,157,193],"hotspot":[104,158],"mutation":[105,159],"was":[106],"knocked":[107],"on":[109,160],"this":[110,161],"background.":[112],"Results:":[113],"Loss":[114],"mutant":[116],"dramatically":[118],"reduced":[119,146],"phosphorylation":[120],"AKT":[122,127,131,189],"proteins":[123,133],"several":[125],"known":[126],"targets,":[128],"but":[129,175],"other":[130],"target":[132],"downstream":[135],"effectors":[136],"mTOR":[138],"were":[139],"not":[140,176],"affected.":[141],"exhibited":[145],"proliferation":[147],"vitro":[149],"vivo.":[152,173],"Knockin":[153],"background":[164],"restored":[165],"signaling,":[167],"proliferation,":[168],"tumor":[170,233],"growth":[171],"PIK3CA,":[174],"mutation,":[178],"increased":[179],"inhibitor":[184,190],"GDC-0941":[185],"allosteric":[188],"MK-2206.":[191],"Conclusions:AKT1":[192],"bona":[196],"fide":[197],"oncogene":[198],"context.":[205],"Distinct":[206],"confer":[210],"differential":[211],"drugs":[214],"at":[218],"different":[219],"points":[220],"by":[222],"mechanisms.":[224],"These":[225],"findings":[226],"implications":[228],"use":[231],"genome":[234],"sequencing":[235],"assign":[237],"patients":[238],"targeted":[240],"Clin":[242],"Cancer":[243],"Res;":[244],"19(19);":[245],"5413\u201322.":[246],"\u00a92013":[247],"AACR.":[248]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2023-04-05T00:00:00"}