{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"submitter":["Jackson ER"],"funding":["ChadTough Foundation","NINDS NIH HHS","National Health and Medical Research Council"],"pubmed_abstract":["Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG. However, further work is needed to identify the mechanisms of response of DIPGs to ONC201 treatment and to determine whether recurring genomic features influence response. Using a systems-biological approach, we showed that ONC201 elicits potent agonism of the mitochondrial protease ClpP to drive proteolysis of electron transport chain and tricarboxylic acid cycle proteins. DIPGs harboring PIK3CA-mutations showed increased sensitivity to ONC201, while tho"],"journal":["Cancer research"],"pagination":["CAN-23-0186"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10345962"],"repository":["biostudies-literature"],"pubmed_title":["ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma."],"pmcid":["PMC10345962"],"funding_grant_id":["GNT1173892","R01 NS119231"],"pubmed_authors":["Skerrett-Byrne DA","Vitanza NA","Findlay IJ","Larsen MR","Yadavilli S","Nazarian J","Pasquier E","Dun MD","Chong WC","Duchatel RJ","Germon ZP","Patabendige A","Cain JE","Smith ND","Nixon B","Gottardo NG","McEwen HP","Endersby R","Colino-Sanguino Y","Hansford JR","Meignan S","Parackal S","Mannan A","Nagabushan S","Valdes-Mora F","Waszak SM","Alvaro F","Eisenstat DD","Staudt DE","Govender D","Howlett M","Jayasekara WSN","McCowage GB","Persson ML","Le Grand M","Day B","Firestein R","Hulleman E","Rakotomalala A","Kearney PS","Manoharan N","Koschmann C","Game S","Andre N","Jackson ER","Beitaki TS","Douglas AM","Mueller S"],"additional_accession":[]},"is_claimable":false,"name":"ONC201 in combination with paxalisib for the treatment of H3K27-altered diffuse midline glioma.","description":"Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are the most lethal of childhood cancers. Palliative radiotherapy is the only established treatment, with median patient survival of 9-11 months. ONC201 is a DRD2 antagonist and ClpP agonist that has shown preclinical and emerging clinical efficacy in DMG. However, further work is needed to identify the mechanisms of response of DIPGs to ONC201 treatment and to determine whether recurring genomic features influence response. Using a systems-biological approach, we showed that ONC201 elicits potent agonism of the mitochondrial protease ClpP to drive proteolysis of electron transport chain and tricarboxylic acid cycle proteins. DIPGs harboring PIK3CA-mutations showed increased sensitivity to ONC201, while tho","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 May","modification":"2026-06-02T10:31:20.139Z","creation":"2026-05-26T03:07:15.998Z"},"accession":"S-EPMC10345962","cross_references":{"pubmed":["37145169"],"doi":["10.1158/0008-5472.CAN-23-0186"]}}