{"id":"https://openalex.org/W4361237862","doi":"https://doi.org/10.1158/0008-5472.c.6507966","title":"Data from Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers","display_name":"Data from Rictor/mTORC2 Drives Progression and Therapeutic Resistance of HER2-Amplified Breast Cancers","publication_year":2023,"publication_date":"2023-03-31","ids":{"openalex":"https://openalex.org/W4361237862","doi":"https://doi.org/10.1158/0008-5472.c.6507966"},"language":"en","primary_location":{"id":"doi:10.1158/0008-5472.c.6507966","doi":"https://doi.org/10.1158/0008-5472.c.6507966","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/0008-5472.c.6507966","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/10.1158/0008-5472.c.6507966","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5054762208","display_name":"Meghan M. Joly","orcid":"https://orcid.org/0009-0003-3329-3321","observed_orcids":["https://orcid.org/0009-0003-3329-3321"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Meghan Morrison Joly","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5041028923","display_name":"Donna J. Hicks","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Donna J. Hicks","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045897963","display_name":"Bayley A. Jones","orcid":"https://orcid.org/0000-0002-8863-4029","observed_orcids":["https://orcid.org/0000-0002-8863-4029"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Bayley Jones","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5037252693","display_name":"Violeta M. Sanchez","orcid":"https://orcid.org/0000-0001-6639-9024","observed_orcids":["https://orcid.org/0000-0001-6639-9024","https://orcid.org/0000-0001-7967-8233"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Violeta Sanchez","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005222149","display_name":"Monica Valeria Estrada","orcid":"https://orcid.org/0000-0001-9846-8223","observed_orcids":["https://orcid.org/0000-0001-9846-8223"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Monica Valeria Estrada","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5050114109","display_name":"Christian D. Young","orcid":"https://orcid.org/0000-0001-9846-488X","observed_orcids":["https://orcid.org/0000-0001-9846-488X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Christian Young","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5069538294","display_name":"Michelle D. Williams","orcid":"https://orcid.org/0000-0002-9133-7332","observed_orcids":["https://orcid.org/0000-0002-9133-7332"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Michelle Williams","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070245444","display_name":"Brent Neil Rexer","orcid":"https://orcid.org/0000-0002-0341-7392","observed_orcids":["https://orcid.org/0000-0002-0341-7392"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Brent N. Rexer","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023663301","display_name":"Dos D. Sarbassov","orcid":"https://orcid.org/0000-0002-6848-1133","observed_orcids":["https://orcid.org/0000-0002-6848-1133"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Dos D. Sarbassov","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061679177","display_name":"William J. Muller","orcid":"https://orcid.org/0000-0001-7690-0695","observed_orcids":["https://orcid.org/0000-0001-7690-0695"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"William J. Muller","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5004009810","display_name":"Dana M. Brantley\u2010Sieders","orcid":"https://orcid.org/0000-0002-2751-6547","observed_orcids":["https://orcid.org/0000-0002-2751-6547","https://orcid.org/0000-0001-9873-6339"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Dana Brantley-Sieders","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5102944784","display_name":"Rebecca S. Cook","orcid":"https://orcid.org/0000-0001-7749-5361","observed_orcids":["https://orcid.org/0000-0001-7749-5361"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Rebecca S. Cook","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/T10755","display_name":"HER2/EGFR in Cancer Research","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/T12829","display_name":"Advanced Breast Cancer Therapies","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/rictor","display_name":"Rictor","score":0.9729999899864197},{"id":"https://openalex.org/keywords/mtorc2","display_name":"mTORC2","score":0.9869999885559082},{"id":"https://openalex.org/keywords/her2-amplified-breast-cancer","display_name":"HER2-amplified breast cancer","score":0.9629999995231628},{"id":"https://openalex.org/keywords/akt-signaling","display_name":"Akt signaling","score":0.7020000219345093},{"id":"https://openalex.org/keywords/akt-s473-phosphorylation","display_name":"AKT S473 phosphorylation","score":0.9679999947547913},{"id":"https://openalex.org/keywords/treatment-resistance","display_name":"treatment resistance","score":0.6850000023841858},{"id":"https://openalex.org/keywords/lapatinib-resistance","display_name":"lapatinib resistance","score":0.9570000171661377},{"id":"https://openalex.org/keywords/raptors","display_name":"raptors","score":0.640999972820282},{"id":"https://openalex.org/keywords/pi3k-signaling","display_name":"PI3K signaling","score":0.7860000133514404},{"id":"https://openalex.org/keywords/tumor-progression","display_name":"tumor progression","score":0.8550000190734863}],"concepts":[{"id":"https://openalex.org/C107846503","wikidata":"https://www.wikidata.org/wiki/Q14876061","display_name":"mTORC2","level":5,"score":0.9583265781402588},{"id":"https://openalex.org/C98490376","wikidata":"https://www.wikidata.org/wiki/Q14876060","display_name":"mTORC1","level":4,"score":0.8529787063598633},{"id":"https://openalex.org/C75217442","wikidata":"https://www.wikidata.org/wiki/Q423650","display_name":"Protein kinase B","level":3,"score":0.7511664628982544},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.7280498147010803},{"id":"https://openalex.org/C86554907","wikidata":"https://www.wikidata.org/wiki/Q285613","display_name":"PI3K/AKT/mTOR pathway","level":3,"score":0.6229575872421265},{"id":"https://openalex.org/C119056186","wikidata":"https://www.wikidata.org/wiki/Q1431332","display_name":"Gene silencing","level":3,"score":0.4231511950492859},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3946884274482727},{"id":"https://openalex.org/C11960822","wikidata":"https://www.wikidata.org/wiki/Q242736","display_name":"Phosphorylation","level":2,"score":0.35919293761253357},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.26368069648742676},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.20727381110191345},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0743781328201294},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/0008-5472.c.6507966","doi":"https://doi.org/10.1158/0008-5472.c.6507966","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/0008-5472.c.6507966","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:10.1158/0008-5472.c.6507966","doi":"https://doi.org/10.1158/0008-5472.c.6507966","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/0008-5472.c.6507966","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":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9537000060081482}],"sustainable_development_goals_aurora":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.6800000071525574}],"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/W2342715069","https://openalex.org/W2567053753","https://openalex.org/W2202926965","https://openalex.org/W2808093573","https://openalex.org/W2341987259","https://openalex.org/W2730375672","https://openalex.org/W7205015213","https://openalex.org/W2792383110","https://openalex.org/W2560959580","https://openalex.org/W4361234588"],"abstract_inverted_index":{"Abstract":[0],"HER2":[1],"overexpression":[2],"drives":[3,176],"Akt":[4,18,21,38,53],"signaling":[5,39,54,175],"and":[6,9,30,111,121,192],"cell":[7,109,135,158],"survival":[8,110],"HER2-enriched":[10],"breast":[11,45,84,102,156,182],"tumors":[12],"have":[13],"a":[14,97],"poor":[15],"outcome":[16],"when":[17],"is":[19,22,40,69],"upregulated.":[20],"activated":[23],"by":[24,152],"phosphorylation":[25,77,112],"at":[26,78,113],"T308":[27],"via":[28,32],"PI3K":[29],"S473":[31,79,114],"mTORC2.":[33],"The":[34],"importance":[35],"of":[36,51,101,106,187],"PI3K-activated":[37],"well":[41],"documented":[42],"in":[43,55,71,138,155,180,198],"HER2-amplified":[44,72,124,181],"cancer":[46,85,157],"models,":[47],"but":[48,160],"the":[49,64,163],"significance":[50],"mTORC2-activated":[52],"this":[56,199],"setting":[57],"remains":[58],"uncertain.":[59],"We":[60,148],"report":[61],"here":[62],"that":[63,173],"mTORC2":[65],"obligate":[66],"cofactor":[67,165],"Rictor":[68,87,107,154],"enriched":[70],"samples,":[73],"correlating":[74],"with":[75,93],"increased":[76],"on":[80,115],"Akt.":[81],"In":[82,96,123],"invasive":[83],"specimens,":[86],"expression":[88],"was":[89],"upregulated":[90],"significantly":[91],"compared":[92],"nonmalignant":[94],"tissues.":[95],"HER2/Neu":[98],"mouse":[99],"model":[100],"cancer,":[103],"genetic":[104],"ablation":[105],"decreased":[108,133],"Akt,":[116],"delaying":[117],"tumor":[118,178],"latency,":[119],"penetrance,":[120],"burden.":[122],"cells,":[125],"exposure":[126],"to":[127,141],"an":[128],"mTORC1/2":[129,189],"dual":[130,188],"kinase":[131,190],"inhibitor":[132],"Akt-dependent":[134,177],"survival,":[136],"including":[137],"cells":[139],"resistant":[140],"lapatinib,":[142],"where":[143],"cytotoxicity":[144],"could":[145],"be":[146],"restored.":[147],"replicated":[149],"these":[150],"findings":[151,171],"silencing":[153,162],"lines,":[159],"not":[161],"mTORC1":[164],"Raptor":[166],"(RPTOR).":[167],"Taken":[168],"together,":[169],"our":[170],"establish":[172],"Rictor/mTORC2":[174],"progression":[179],"cancers,":[183],"rationalizing":[184],"clinical":[185],"investigation":[186],"inhibitors":[191,195],"developing":[193],"mTORC2-specific":[194],"for":[196],"use":[197],"setting.":[200],"Cancer":[201],"Res;":[202],"76(16);":[203],"4752\u201364.":[204],"\u00a92016":[205],"AACR.":[206]},"counts_by_year":[],"updated_date":"2026-09-24T07:57:37.273135","created_date":"2023-03-31T00:00:00"}