{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Maynard RE"],"funding":["NCI NIH HHS","Johns Hopkins University School of Medicine","NIGMS NIH HHS"],"pagination":["137-145"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9195565"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["504"],"pubmed_abstract":["Medulloblastoma is the most common malignant pediatric brain tumor. Tumors having high levels of c-MYC have the worst clinical prognosis, with only a minority of patients surviving. To address this unmet clinical need, we generated a human neural stem cell model of medulloblastoma that recapitulated the most aggressive subtype phenotypically and by mRNA expression profiling. An in silico analysis of these cells identified mTOR inhibitors as potential therapeutic agents. We hypothesized that the orally bioavailable TORC1/2 kinase inhibitor TAK228 would have activity against MYC-driven medulloblastoma. TAK228 inhibited mTORC1/2, decreased cell growth and caused apoptosis in high-MYC medulloblastoma cell lines. Comprehensive metabolic profiling of medulloblastoma orthotopic xenografts showed "],"journal":["Cancer letters"],"pubmed_title":["TORC1/2 kinase inhibition depletes glutathione and synergizes with carboplatin to suppress the growth of MYC-driven medulloblastoma."],"pmcid":["PMC9195565"],"funding_grant_id":["P30 CA006973","R01 GM074024","U01 CA217885","U01 CA184898","U24 CA220341","U54 CA209891","U24 CA194107"],"pubmed_authors":["Pham K","Pomeroy SL","Archer TC","Poore B","Tamayo P","Eberhart CG","Maynard RE","Hanaford AR","James M","Park Y","Slusher BS","Alt J","Mesirov J","Raabe EH"],"additional_accession":[]},"is_claimable":false,"name":"TORC1/2 kinase inhibition depletes glutathione and synergizes with carboplatin to suppress the growth of MYC-driven medulloblastoma.","description":"Medulloblastoma is the most common malignant pediatric brain tumor. Tumors having high levels of c-MYC have the worst clinical prognosis, with only a minority of patients surviving. To address this unmet clinical need, we generated a human neural stem cell model of medulloblastoma that recapitulated the most aggressive subtype phenotypically and by mRNA expression profiling. An in silico analysis of these cells identified mTOR inhibitors as potential therapeutic agents. We hypothesized that the orally bioavailable TORC1/2 kinase inhibitor TAK228 would have activity against MYC-driven medulloblastoma. TAK228 inhibited mTORC1/2, decreased cell growth and caused apoptosis in high-MYC medulloblastoma cell lines. Comprehensive metabolic profiling of medulloblastoma orthotopic xenografts showed ","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Apr","modification":"2025-04-25T19:44:21.563Z","creation":"2025-04-06T08:10:04.57Z"},"accession":"S-EPMC9195565","cross_references":{"pubmed":["33571541"],"doi":["10.1016/j.canlet.2021.02.001"]}}