<> <http://www.w3.org/2000/01/rdf-schema#comment> "The repository administrator has not yet configured an RDF license."^^<http://www.w3.org/2001/XMLSchema#string> . <> <http://xmlns.com/foaf/0.1/primaryTopic> <https://discovery.ucl.ac.uk/id/eprint/10144763> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/AcademicArticle> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Article> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/dc/terms/title> "Combination of BMI1 and MAPK/ERK inhibitors is effective in medulloblastoma"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/ontology/bibo/abstract> "BACKGROUND: Epigenetic changes play a key role in the pathogenesis of medulloblastoma (MB), the most common malignant paediatric brain tumour. METHODS: We explore the therapeutic potential of BMI1 and MAPK/ERK inhibition in BMI1 High;CHD7 Low MB cells and in a pre-clinical xenograft model. RESULTS: We identify a synergistic vulnerability of BMI1 High;CHD7 Low MB cells to a combination treatment with BMI1 and MAPK/ERK inhibitors. Mechanistically, CHD7-dependent binding of BMI1 to MAPK-regulated genes underpins the CHD7-BMI1-MAPK regulatory axis responsible of the anti-tumour effect of the inhibitors in vitro and in a pre-clinical mouse model. Increased ERK1 and ERK2 phosphorylation activity is found in BMI1 High;CHD7 Low G4 MB patients, raising the possibility that they could be amenable to a similar therapy. CONCLUSIONS: The molecular dissection of the CHD7-BMI1-MAPK regulatory axis in BMI1 High;CHD7 Low MB identifies this signature as a proxy to predict MAPK functional activation, which can be effectively drugged in preclinical models, and paves the way for further exploration of combined BMI1 and MAPK targeting in G4 MB patients."^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/dc/terms/date> "2022-02-25" . <https://discovery.ucl.ac.uk/id/document/1452483> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://purl.org/ontology/bibo/Document> . <https://discovery.ucl.ac.uk/id/org/ext-daeb92daf570917684167066877da0ed> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Organization> . <https://discovery.ucl.ac.uk/id/org/ext-daeb92daf570917684167066877da0ed> <http://xmlns.com/foaf/0.1/name> "Oxford University Press (OUP)"^^<http://www.w3.org/2001/XMLSchema#string> . 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<https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> . <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_1> <https://discovery.ucl.ac.uk/id/person/ext-aa93f33fcb42608bc55415c1ad9e60c6> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-daaa7e35ee4ff0ce27b60f2fadb365a8> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> . <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_2> <https://discovery.ucl.ac.uk/id/person/ext-daaa7e35ee4ff0ce27b60f2fadb365a8> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-52225ee148e45b9c88d56728ecd5c5a9> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> . <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_3> <https://discovery.ucl.ac.uk/id/person/ext-52225ee148e45b9c88d56728ecd5c5a9> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-e352be8deeb4359179f7ab22ca4a16f8> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> . <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_4> <https://discovery.ucl.ac.uk/id/person/ext-e352be8deeb4359179f7ab22ca4a16f8> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-c8957b4ae2398c0c09c9be3a44bc9f17> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> . <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_5> <https://discovery.ucl.ac.uk/id/person/ext-c8957b4ae2398c0c09c9be3a44bc9f17> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-27118cb41e2a1b35e593f406f8ea0fa8> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> . <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_6> <https://discovery.ucl.ac.uk/id/person/ext-27118cb41e2a1b35e593f406f8ea0fa8> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-203781f9a8ac212f508562de12756d3e> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> . <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_7> <https://discovery.ucl.ac.uk/id/person/ext-203781f9a8ac212f508562de12756d3e> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-dc06ac9a767af5bf05e80de9dff49d24> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> . <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_8> <https://discovery.ucl.ac.uk/id/person/ext-dc06ac9a767af5bf05e80de9dff49d24> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/dc/terms/creator> <https://discovery.ucl.ac.uk/id/person/ext-a8ffb00da18c792c59c6cd3b5d44e091> . <https://discovery.ucl.ac.uk/id/eprint/10144763> <http://purl.org/ontology/bibo/authorList> <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> . <https://discovery.ucl.ac.uk/id/eprint/10144763#authors> <http://www.w3.org/1999/02/22-rdf-syntax-ns#_9> <https://discovery.ucl.ac.uk/id/person/ext-a8ffb00da18c792c59c6cd3b5d44e091> . <https://discovery.ucl.ac.uk/id/person/ext-c8957b4ae2398c0c09c9be3a44bc9f17> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-c8957b4ae2398c0c09c9be3a44bc9f17> <http://xmlns.com/foaf/0.1/givenName> "Gillian"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-c8957b4ae2398c0c09c9be3a44bc9f17> <http://xmlns.com/foaf/0.1/familyName> "Morrison"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-c8957b4ae2398c0c09c9be3a44bc9f17> <http://xmlns.com/foaf/0.1/name> "Gillian Morrison"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-e352be8deeb4359179f7ab22ca4a16f8> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-e352be8deeb4359179f7ab22ca4a16f8> <http://xmlns.com/foaf/0.1/givenName> "Sebastian"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-e352be8deeb4359179f7ab22ca4a16f8> <http://xmlns.com/foaf/0.1/familyName> "Brandner"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-e352be8deeb4359179f7ab22ca4a16f8> <http://xmlns.com/foaf/0.1/name> "Sebastian Brandner"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-daaa7e35ee4ff0ce27b60f2fadb365a8> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-daaa7e35ee4ff0ce27b60f2fadb365a8> <http://xmlns.com/foaf/0.1/givenName> "Nicola"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-daaa7e35ee4ff0ce27b60f2fadb365a8> <http://xmlns.com/foaf/0.1/familyName> "Pomella"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-daaa7e35ee4ff0ce27b60f2fadb365a8> <http://xmlns.com/foaf/0.1/name> "Nicola Pomella"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-27118cb41e2a1b35e593f406f8ea0fa8> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-27118cb41e2a1b35e593f406f8ea0fa8> <http://xmlns.com/foaf/0.1/givenName> "Steven M"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-27118cb41e2a1b35e593f406f8ea0fa8> <http://xmlns.com/foaf/0.1/familyName> "Pollard"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-27118cb41e2a1b35e593f406f8ea0fa8> <http://xmlns.com/foaf/0.1/name> "Steven M Pollard"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-52225ee148e45b9c88d56728ecd5c5a9> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-52225ee148e45b9c88d56728ecd5c5a9> <http://xmlns.com/foaf/0.1/givenName> "Yau Mun"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-52225ee148e45b9c88d56728ecd5c5a9> <http://xmlns.com/foaf/0.1/familyName> "Lim"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-52225ee148e45b9c88d56728ecd5c5a9> <http://xmlns.com/foaf/0.1/name> "Yau Mun Lim"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-dc06ac9a767af5bf05e80de9dff49d24> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-dc06ac9a767af5bf05e80de9dff49d24> <http://xmlns.com/foaf/0.1/givenName> "Nicolae Radu"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-dc06ac9a767af5bf05e80de9dff49d24> <http://xmlns.com/foaf/0.1/familyName> "Zabet"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-dc06ac9a767af5bf05e80de9dff49d24> <http://xmlns.com/foaf/0.1/name> "Nicolae Radu Zabet"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-a8ffb00da18c792c59c6cd3b5d44e091> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-a8ffb00da18c792c59c6cd3b5d44e091> <http://xmlns.com/foaf/0.1/givenName> "Silvia"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-a8ffb00da18c792c59c6cd3b5d44e091> <http://xmlns.com/foaf/0.1/familyName> "Marino"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-a8ffb00da18c792c59c6cd3b5d44e091> <http://xmlns.com/foaf/0.1/name> "Silvia Marino"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-203781f9a8ac212f508562de12756d3e> <http://www.w3.org/1999/02/22-rdf-syntax-ns#type> <http://xmlns.com/foaf/0.1/Person> . <https://discovery.ucl.ac.uk/id/person/ext-203781f9a8ac212f508562de12756d3e> <http://xmlns.com/foaf/0.1/givenName> "Xinyu"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-203781f9a8ac212f508562de12756d3e> <http://xmlns.com/foaf/0.1/familyName> "Zhang"^^<http://www.w3.org/2001/XMLSchema#string> . <https://discovery.ucl.ac.uk/id/person/ext-203781f9a8ac212f508562de12756d3e> <http://xmlns.com/foaf/0.1/name> "Xinyu Zhang"^^<http://www.w3.org/2001/XMLSchema#string> . 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