{"doi":"10.1016/j.bbrc.2013.07.014","title":"Reactivation of AKT signaling following treatment of cancer cells with PI3K inhibitors attenuates their antitumor effects","abstract":null,"journal":"Biochemical and Biophysical Research Communications","year":2013,"id":592699,"datarank":1.0404949582420002,"base_score":3.091042453358316,"endowment":3.091042453358316,"self_citation_contribution":0.4636563680037475,"citation_network_contribution":0.5768385902382528,"self_endowment_contribution":0.4636563680037475,"citer_contribution":0.5768385902382528,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":18,"citers_with_citation_signal":18,"citers_with_endowment":18,"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":1516719,"name":"Anne Dormond-Meuwly","orcid":null,"position":1,"is_corresponding":false},{"id":1516720,"name":"Catherine Pythoud","orcid":null,"position":2,"is_corresponding":false},{"id":65972,"name":"Nicolas Demartines","orcid":"0000-0002-1530-3114","position":3,"is_corresponding":false},{"id":1516721,"name":"Olivier Dormond","orcid":null,"position":4,"is_corresponding":false},{"id":1516718,"name":"Marc Dufour","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Reactivation of AKT signaling following treatment of cancer cells with PI3K inhibitors attenuates their antitumor effects","abstract":"Targeting the phosphatidylinositol-3-kinase (PI3K) is a promising approach in cancer therapy. In particular, PI3K blockade leads to the inhibition of AKT, a major downstream effector responsible for the oncogenic activity of PI3K. However, we report here that small molecule inhibitors of PI3K only transiently block AKT signaling. Indeed, treatment of cancer cells with PI3K inhibitors results in a rapid inhibition of AKT phosphorylation and signaling which is followed by the reactivation of AKT signaling after 48 h as observed by Western blot. Reactivation of AKT signaling occurs despite effective inhibition of PI3K activity by PI3K inhibitors. In addition, wortmannin, a broad range PI3K inhibitor, did not block AKT reactivation suggesting that AKT signals independently of PI3K. In a therapeutical perspective, combining AKT and PI3K inhibitors exhibit stronger anti-proliferative and pro-apoptotic effects compared to AKT or PI3K inhibitors alone. Similarly, in a tumor xenograft mouse model, concomitant PI3K and AKT blockade results in stronger anti-cancer activity compared with either blockade alone. This study shows that PI3K inhibitors only transiently inhibit AKT which limits their antitumor activities. It also provides the proof of concept to combine PI3K inhibitors with AKT inhibitors in cancer therapy.","is_dataset_classified":null,"base_score":3.091042453358316,"endowment":3.091042453358316,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23867821","pmcid":null,"openalex_id":"https://openalex.org/W2070783513","authors":[],"funders":[{"funder_name":"Swiss National Science Foundation","grant_id":"SCORE 32323B-123821","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"32323B-139788","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"139788","title":"Role of mTORC2 in angiogenesis"},{"funder_name":"Novartis Foundation for Medical and Biological Research","grant_id":"","title":null}],"total_grants":4,"fwci":0.295,"citation_percentile":0.61793003,"influential_citations":0,"citation_trend":[{"year":2015,"count":2},{"year":2017,"count":5},{"year":2018,"count":1},{"year":2019,"count":2},{"year":2021,"count":4},{"year":2022,"count":1},{"year":2023,"count":3},{"year":2024,"count":1},{"year":2025,"count":2}],"oa_status":"closed","license":"Elsevier TDM","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0006291X13011546?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0006291X13011546?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.bbrc.2013.07.014","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23867821","host_type":"repository"},{"url":"https://iris.unil.ch/handle/iris/71599","host_type":"repository"},{"url":"https://serval.unil.ch/notice/serval:BIB_37BE773A7D11","host_type":"repository"},{"url":"https://dx.doi.org/10.1016/j.bbrc.2013.07.014","host_type":""},{"url":"https://sonar.ch/global/documents/27054","host_type":""},{"url":"http://dx.doi.org/10.1016/j.bbrc.2013.07.014","host_type":""}],"fields_of_study":["PI3K/AKT/mTOR signaling in cancer","Mast cells and histamine","Cancer Mechanisms and Therapy","0301 basic medicine","0303 health sciences","03 medical and health sciences","Androstadienes","Antineoplastic Agents","Apoptosis","Cell Line, Tumor","Enzyme Activation","Humans","Neoplasms, Experimental","PTEN Phosphohydrolase","Phosphoinositide-3 Kinase Inhibitors","Proto-Oncogene Proteins c-akt","Signal Transduction","Wortmannin"],"mesh_terms":["Wortmannin","Phosphoinositide-3 Kinase Inhibitors","Androstadienes","Antineoplastic Agents","Enzyme Activation","Humans","Neoplasms, Experimental","Signal Transduction","Apoptosis","Cell Line, Tumor","Proto-Oncogene Proteins c-akt","PTEN Phosphohydrolase"],"keywords":["PI3K/AKT/mTOR pathway","Protein kinase B","Wortmannin","Phosphorylation","Cancer research","Chemistry","Signal transduction","Cancer","Pharmacology","Biology","Medicine","Biochemistry","Internal medicine","Resistance","Signaling","PTEN","PI3K","phosphatidylinositol-3-kinase","AKT","Pi3k Inhibitors","Phosphatase And Tensin Homolog","PTEN Phosphohydrolase","Antineoplastic Agents","Apoptosis","Neoplasms, Experimental","Androstadienes","Enzyme Activation","Cell Line, Tumor","Humans","Proto-Oncogene Proteins c-akt","Phosphoinositide-3 Kinase Inhibitors"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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