{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["7(36)"],"submitter":["Venkatesan S"],"pubmed_abstract":["<h4>Background</h4>Glioblastoma is the most malignant tumor of the central nervous system and still lacks effective treatment. This study explores mutational biomarkers of 11 drugs targeting either the RTK/Ras/PI3K, the p53 or the Rb pathway using 25 patient-derived glioblastoma stem-like cell cultures (GSCs).<h4>Results</h4>We found that TP53 mutated GSCs were approximately 3.5 fold more sensitive to dual inhibition of mammalian target of rapamycin complex 1 and 2 (mTORC1/2) compared to wild type GSCs. We identified that Bcl-2(Thr56/Ser70) phosphorylation contributed to the resistance of TP53 wild type GSCs against dual mTORC1/2 inhibition. The Bcl-2 inhibitor ABT-263 (navitoclax) increased sensitivity to the mTORC1/2 inhibitor AZD8055 in TP53 wild type GSCs, while sensitivity to AZD8055 "],"journal":["Oncotarget"],"pagination":["58435-58444"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5295441"],"repository":["biostudies-literature"],"pubmed_title":["TP53 mutated glioblastoma stem-like cell cultures are sensitive to dual mTORC1/2 inhibition while resistance in TP53 wild type cultures can be overcome by combined inhibition of mTORC1/2 and Bcl-2."],"pmcid":["PMC5295441"],"pubmed_authors":["Martens JW","Leenstra S","Pierson T","Besselink NJ","Dubbink HJ","Hoogstraat M","Dekker LJ","Caljouw E","Zeneyedpour L","Lamfers ML","Joore J","van der Kaaij M","Luider TM","Spoor JK","Berghauser Pont LM","Sleijfer S","Venkatesan S","Kloezeman J"],"additional_accession":[]},"is_claimable":false,"name":"TP53 mutated glioblastoma stem-like cell cultures are sensitive to dual mTORC1/2 inhibition while resistance in TP53 wild type cultures can be overcome by combined inhibition of mTORC1/2 and Bcl-2.","description":"<h4>Background</h4>Glioblastoma is the most malignant tumor of the central nervous system and still lacks effective treatment. This study explores mutational biomarkers of 11 drugs targeting either the RTK/Ras/PI3K, the p53 or the Rb pathway using 25 patient-derived glioblastoma stem-like cell cultures (GSCs).<h4>Results</h4>We found that TP53 mutated GSCs were approximately 3.5 fold more sensitive to dual inhibition of mammalian target of rapamycin complex 1 and 2 (mTORC1/2) compared to wild type GSCs. We identified that Bcl-2(Thr56/Ser70) phosphorylation contributed to the resistance of TP53 wild type GSCs against dual mTORC1/2 inhibition. The Bcl-2 inhibitor ABT-263 (navitoclax) increased sensitivity to the mTORC1/2 inhibitor AZD8055 in TP53 wild type GSCs, while sensitivity to AZD8055 ","dates":{"release":"2016-01-01T00:00:00Z","publication":"2016 Sep","modification":"2026-05-05T15:00:45.613Z","creation":"2019-03-27T02:35:56Z"},"accession":"S-EPMC5295441","cross_references":{"pubmed":["27533080"],"doi":["10.18632/oncotarget.11205"]}}