{"id":"https://openalex.org/W7117239586","doi":"https://doi.org/10.5455/annalsmedres.2025.07.185","title":"In Silico Characterization of Missense Mutations in PI3K/AKT/mTOR Signaling Genes in Breast Cancer and Their Role in Therapeutic Resistance","display_name":"In Silico Characterization of Missense Mutations in PI3K/AKT/mTOR Signaling Genes in Breast Cancer and Their Role in Therapeutic Resistance","publication_year":2025,"publication_date":"2025-01-01","ids":{"openalex":"https://openalex.org/W7117239586","doi":"https://doi.org/10.5455/annalsmedres.2025.07.185"},"language":"en","primary_location":{"id":"doi:10.5455/annalsmedres.2025.07.185","doi":"https://doi.org/10.5455/annalsmedres.2025.07.185","is_oa":true,"landing_page_url":"https://doi.org/10.5455/annalsmedres.2025.07.185","pdf_url":null,"source":{"id":"https://openalex.org/S4210239751","display_name":"Annals of Medical Research","issn_l":"1300-1744","issn":["1300-1744","2636-7688"],"is_oa":true,"is_in_doaj":true,"is_core":false,"listed_in":["doaj","tr-dizin"],"host_organization":"https://openalex.org/P4360969463","host_organization_name":"Inonu University Faculty of Medicine","host_organization_lineage":["https://openalex.org/P4360969463"],"host_organization_lineage_names":["Inonu University Faculty of Medicine"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Annals of Medical Research","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"diamond","oa_url":"https://doi.org/10.5455/annalsmedres.2025.07.185","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5060439851","display_name":"Bet\u00fcl Ak\u00e7e\u015fme","orcid":"https://orcid.org/0000-0002-3730-9963","observed_orcids":["https://orcid.org/0000-0002-3730-9963"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Bet\u00fcl Ak\u00e7e\u015fme","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5092473517","display_name":"Haris Lokvan\u010di\u0107","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Haris Lokvan\u010di\u0107","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5054294371","display_name":"Nadia Islam","orcid":"https://orcid.org/0009-0007-3920-1140","observed_orcids":["https://orcid.org/0009-0007-3920-1140"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Nadia Islam","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":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"32","issue":"12","first_page":"541","last_page":"541"},"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":0.9990000128746033,"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":0.9990000128746033,"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/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.000699999975040555,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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/T11642","display_name":"Genomics and Rare Diseases","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"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/breast-cancer","display_name":"breast cancer","score":0.8700000047683716},{"id":"https://openalex.org/keywords/pi3k-akt-mtor-pathway","display_name":"PI3K/AKT/mTOR pathway","score":0.8920000195503235},{"id":"https://openalex.org/keywords/missense-mutations","display_name":"missense mutations","score":1.0},{"id":"https://openalex.org/keywords/treatment-resistance","display_name":"treatment resistance","score":0.871999979019165},{"id":"https://openalex.org/keywords/pten","display_name":"PTEN","score":0.7889999747276306},{"id":"https://openalex.org/keywords/akt1","display_name":"AKT1","score":0.9919999837875366},{"id":"https://openalex.org/keywords/akt2","display_name":"AKT2","score":1.0},{"id":"https://openalex.org/keywords/deleterious-variant-prediction","display_name":"deleterious variant prediction","score":0.8240000009536743},{"id":"https://openalex.org/keywords/tumor-cell-survival","display_name":"tumor cell survival","score":0.6520000100135803},{"id":"https://openalex.org/keywords/risk-stratification-biomarkers","display_name":"risk stratification biomarkers","score":0.796999990940094},{"id":"https://openalex.org/keywords/therapeutic-target","display_name":"therapeutic target","score":0.7039999961853027}],"concepts":[{"id":"https://openalex.org/C75563809","wikidata":"https://www.wikidata.org/wiki/Q2656896","display_name":"Missense mutation","level":4,"score":0.7935000061988831},{"id":"https://openalex.org/C2777609662","wikidata":"https://www.wikidata.org/wiki/Q416356","display_name":"PTEN","level":4,"score":0.7020999789237976},{"id":"https://openalex.org/C2775905019","wikidata":"https://www.wikidata.org/wiki/Q192572","display_name":"In silico","level":3,"score":0.6995000243186951},{"id":"https://openalex.org/C530470458","wikidata":"https://www.wikidata.org/wiki/Q128581","display_name":"Breast cancer","level":3,"score":0.6923999786376953},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5903000235557556},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.5591999888420105},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.4620000123977661},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.435699999332428},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.4180000126361847},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.4083000123500824},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.3928000032901764},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.3871999979019165},{"id":"https://openalex.org/C154137905","wikidata":"https://www.wikidata.org/wiki/Q17816452","display_name":"AKT1","level":4,"score":0.3476000130176544},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.34529998898506165},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.3375999927520752},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.27230000495910645},{"id":"https://openalex.org/C88216763","wikidata":"https://www.wikidata.org/wiki/Q4652205","display_name":"AKT2","level":5,"score":0.27000001072883606},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.26170000433921814},{"id":"https://openalex.org/C2781230642","wikidata":"https://www.wikidata.org/wiki/Q492646","display_name":"Targeted therapy","level":3,"score":0.26159998774528503},{"id":"https://openalex.org/C105951970","wikidata":"https://www.wikidata.org/wiki/Q1036748","display_name":"Loss function","level":4,"score":0.2587999999523163}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.5455/annalsmedres.2025.07.185","doi":"https://doi.org/10.5455/annalsmedres.2025.07.185","is_oa":true,"landing_page_url":"https://doi.org/10.5455/annalsmedres.2025.07.185","pdf_url":null,"source":{"id":"https://openalex.org/S4210239751","display_name":"Annals of Medical Research","issn_l":"1300-1744","issn":["1300-1744","2636-7688"],"is_oa":true,"is_in_doaj":true,"is_core":false,"listed_in":["doaj","tr-dizin"],"host_organization":"https://openalex.org/P4360969463","host_organization_name":"Inonu University Faculty of Medicine","host_organization_lineage":["https://openalex.org/P4360969463"],"host_organization_lineage_names":["Inonu University Faculty of Medicine"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Annals of Medical Research","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.5455/annalsmedres.2025.07.185","doi":"https://doi.org/10.5455/annalsmedres.2025.07.185","is_oa":true,"landing_page_url":"https://doi.org/10.5455/annalsmedres.2025.07.185","pdf_url":null,"source":{"id":"https://openalex.org/S4210239751","display_name":"Annals of Medical Research","issn_l":"1300-1744","issn":["1300-1744","2636-7688"],"is_oa":true,"is_in_doaj":true,"is_core":false,"listed_in":["doaj","tr-dizin"],"host_organization":"https://openalex.org/P4360969463","host_organization_name":"Inonu University Faculty of Medicine","host_organization_lineage":["https://openalex.org/P4360969463"],"host_organization_lineage_names":["Inonu University Faculty of Medicine"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Annals of Medical Research","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9763000011444092,"display_name":"Good health and well-being"}],"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/W3170823416","https://openalex.org/W2921329853","https://openalex.org/W2332344270","https://openalex.org/W4412642237","https://openalex.org/W3132240246","https://openalex.org/W4417231788","https://openalex.org/W4388717209","https://openalex.org/W2079120139","https://openalex.org/W2071322951","https://openalex.org/W4313472063"],"abstract_inverted_index":{"Aim:":[0],"This":[1],"study":[2],"aimed":[3],"to":[4,19,64,106,108,153,162],"investigate":[5],"the":[6,15,25,31,49,66,129,155,164],"most":[7],"frequent":[8],"missense":[9,71],"mutations":[10,81,160],"in":[11,24,48,120,169],"key":[12],"genes":[13,46],"of":[14,27,33,60,70,132,158,166],"PI3K/AKT/mTOR":[16,50,110],"signalling":[17],"pathway":[18,51,77,111],"evaluate":[20],"their":[21],"potential":[22,136],"role":[23],"progression":[26],"breast":[28,121,133,170],"cancer":[29,114],"and":[30,40,56,76,95,99,117,141,148,161],"development":[32,165],"therapy":[34],"resistance":[35,119],"using":[36],"computational":[37,61],"analyses.":[38],"Materials":[39],"Methods:":[41],"We":[42],"systematically":[43],"analysed":[44],"nine":[45],"involved":[47],"by":[52],"screening":[53],"mutation":[54],"databases":[55],"applying":[57],"a":[58],"range":[59],"prediction":[62],"tools":[63],"assess":[65],"possible":[67],"deleterious":[68,84],"effects":[69,85],"variants":[72,103],"on":[73],"protein":[74],"function":[75],"regulation.":[78],"Results:":[79],"Several":[80],"with":[82],"predicted":[83,105],"were":[86,104,151],"identified,":[87],"including":[88],"PTEN":[89],"(D92H,":[90],"D92N,":[91],"R130G,":[92],"R130Q,":[93],"C136R,":[94],"C136Y),":[96],"AKT1":[97],"(L52R),":[98],"AKT2":[100],"(R170W).":[101],"These":[102],"contribute":[107],"aberrant":[109],"activation,":[112],"enhanced":[113],"cell":[115],"survival,":[116],"therapeutic":[118,143],"cancer.":[122,171],"Conclusion:":[123],"The":[124],"findings":[125],"provided":[126],"insights":[127],"into":[128],"mutational":[130],"landscape":[131],"cancer,":[134],"suggesting":[135],"biomarkers":[137],"for":[138],"risk":[139],"stratification":[140],"novel":[142],"targets.":[144],"Further":[145],"experimental":[146],"validation":[147],"functional":[149],"studies":[150],"recommended":[152],"clarify":[154],"clinical":[156],"significance":[157],"these":[159],"guide":[163],"personalised":[167],"interventions":[168]},"counts_by_year":[],"updated_date":"2026-11-13T13:42:25.865203","created_date":"2025-12-25T00:00:00"}