{"doi":"10.1172/jci44145","title":"Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy","abstract":null,"journal":"Journal of Clinical Investigation","year":2011,"id":657826,"datarank":12.20933718379924,"base_score":6.040254711277414,"endowment":6.040254711277414,"self_citation_contribution":0.9060382066916122,"citation_network_contribution":11.303298977107628,"self_endowment_contribution":0.9060382066916122,"citer_contribution":11.303298977107628,"corpus_percentile":null,"corpus_rank":null,"citation_count":419,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":609918,"name":"Bryan T. Hennessy","orcid":"0000-0002-7871-6477","position":1,"is_corresponding":false},{"id":269703,"name":"Joyce M. Slingerland","orcid":"0000-0003-1487-8554","position":2,"is_corresponding":false},{"id":3745,"name":"Seth A. Wander","orcid":"0000-0002-4127-4708","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy","abstract":"Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.","is_dataset_classified":null,"base_score":6.040254711277414,"endowment":6.040254711277414,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"21490404","pmcid":null,"openalex_id":"https://openalex.org/W2025935112","authors":[],"funders":[{"funder_name":"National Institutes of Health","grant_id":"5R01CA105118-04","title":"PI3K opposes p27 and G1 arrest by TGF-B in human cancer"}],"total_grants":1,"fwci":17.1412,"citation_percentile":0.99597855,"influential_citations":0,"citation_trend":[{"year":2012,"count":28},{"year":2013,"count":48},{"year":2014,"count":50},{"year":2015,"count":63},{"year":2016,"count":26},{"year":2017,"count":39},{"year":2018,"count":26},{"year":2019,"count":21},{"year":2020,"count":23},{"year":2021,"count":14},{"year":2022,"count":16},{"year":2023,"count":19},{"year":2024,"count":10},{"year":2025,"count":15},{"year":2026,"count":4}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"http://www.jci.org/articles/view/44145/files/pdf","host_type":"journal"},{"url":"http://www.jci.org/articles/view/44145/files/pdf","host_type":"publisher"},{"url":"https://doi.org/10.1172/jci44145","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/21490404","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3069769","host_type":"repository"},{"url":"http://hdl.handle.net/10147/230660","host_type":"repository"},{"url":"https://dx.doi.org/10.1172/jci44145","host_type":""},{"url":"https://hdl.handle.net/10147/230660","host_type":""}],"fields_of_study":["PI3K/AKT/mTOR signaling in cancer","Microtubule and mitosis dynamics","Protein Kinase Regulation and GTPase Signaling","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Tuberous Sclerosis Complex 1 Protein","Tuberous Sclerosis Complex 2 Protein","Phosphoinositide-3 Kinase Inhibitors","Antineoplastic Agents","Clinical Trials as Topic","Female","Humans","Male","Neoplasms","Transcription Factors","Signal Transduction","Phosphatidylinositol 3-Kinases","Sirolimus","Tumor Suppressor Proteins","Protein Kinase Inhibitors","TOR Serine-Threonine Kinases"],"keywords":["mTORC1","PI3K/AKT/mTOR pathway","mTORC2","Mechanistic target of rapamycin","Cancer research","RPTOR","Discovery and development of mTOR inhibitors","Sirolimus","Biology","Signal transduction","Cell growth","Bioinformatics","Medicine","Cell biology","Genetics","Internal medicine","Male","Clinical Trials as Topic","TOR Serine-Threonine Kinases","Tumor Suppressor Proteins","Antineoplastic Agents","Tuberous Sclerosis Complex 1 Protein","Phosphatidylinositol 3-Kinases","Neoplasms","Tuberous Sclerosis Complex 2 Protein","Humans","Female","Protein Kinase Inhibitors","Phosphoinositide-3 Kinase Inhibitors","Transcription Factors"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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