{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kelly LM"],"funding":["Fondation Bettencourt Schueller (Bettencourt Schueller Foundation)","European Research Council","NCI NIH HHS","U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM)","U.S. Department of Health & Human Services | National Institutes of Health (NIH)","Institut National Du Cancer (French National Cancer Institute)","NIGMS NIH HHS"],"pagination":["1082-1101"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11778622"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(7)"],"pubmed_abstract":["Dose-limiting toxicity poses a major limitation to the clinical utility of targeted cancer therapies, often arising from target engagement in nonmalignant tissues. This obstacle can be minimized by targeting cancer dependencies driven by proteins with tissue-restricted and/or tumor-restricted expression. In line with another recent report, we show here that, in acute myeloid leukemia (AML), suppression of the myeloid-restricted PIK3CG/p110γ-PIK3R5/p101 axis inhibits protein kinase B/Akt signaling and compromises AML cell fitness. Furthermore, silencing the genes encoding PIK3CG/p110γ or PIK3R5/p101 sensitizes AML cells to established AML therapies. Importantly, we find that existing small-molecule inhibitors against PIK3CG are insufficient to achieve a sustained long-term antileukemic effe"],"journal":["Nature cancer"],"pubmed_title":["Targeting a lineage-specific PI3Kɣ-Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule."],"pmcid":["PMC11778622"],"funding_grant_id":["R01 CA266389","U54 CA274502","PLBIO20-074","SIRIC InsiTu program (INCa-DGOS-INSERM-ITMO Cancer_18008)","CCA INSERM Bettencourt","PLBIO20-246","R01CA266389","5U54CA274502-02","758848","P41 GM103504","101088563"],"pubmed_authors":["Kelly LM","Carretero E","Benajiba L","Loew D","Lin KH","Ades L","Charles J","Latour E","Fenouille N","Killarney ST","Martin AR","Puissant A","Arang N","Amblard M","Raffoux E","Rutter JC","Ling F","Lobry C","Ang HX","Huynh T","Ho Nhat D","Fodil S","Krogan NJ","Namor F","Brunel L","Forget A","Culeux C","Pasquer H","Sebert M","Swaney DL","Itzykson R","Duchmann M","Verdie P","Wood KC","Lombard B"],"additional_accession":[]},"is_claimable":false,"name":"Targeting a lineage-specific PI3Kɣ-Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule.","description":"Dose-limiting toxicity poses a major limitation to the clinical utility of targeted cancer therapies, often arising from target engagement in nonmalignant tissues. This obstacle can be minimized by targeting cancer dependencies driven by proteins with tissue-restricted and/or tumor-restricted expression. In line with another recent report, we show here that, in acute myeloid leukemia (AML), suppression of the myeloid-restricted PIK3CG/p110γ-PIK3R5/p101 axis inhibits protein kinase B/Akt signaling and compromises AML cell fitness. Furthermore, silencing the genes encoding PIK3CG/p110γ or PIK3R5/p101 sensitizes AML cells to established AML therapies. Importantly, we find that existing small-molecule inhibitors against PIK3CG are insufficient to achieve a sustained long-term antileukemic effe","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2026-06-01T22:08:59.259Z","creation":"2026-05-22T03:08:31.688Z"},"accession":"S-EPMC11778622","cross_references":{"pubmed":["38816660"],"doi":["10.1038/s43018-024-00782-5"]}}