dc.creator | Pladevall Morera, David | es |
dc.creator | Castejón Griñán, María | es |
dc.creator | Aguilera, Paula | es |
dc.creator | Gaardahl, Karina | es |
dc.creator | Ingham, Andreas | es |
dc.creator | Brosnan Cashman, Jacqueline A. | es |
dc.creator | Meeker, Alan K. | es |
dc.creator | López Contreras, Andrés J. | es |
dc.date.accessioned | 2022-04-20T07:32:51Z | |
dc.date.available | 2022-04-20T07:32:51Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Pladevall Morera, D., Castejón Griñán, M., Aguilera, P., Gaardahl, K., Ingham, ., Brosnan Cashman, J.A.,...,López Contreras, A.J. (2022). ATRX-Deficient High-Grade Glioma Cells Exhibit Increased Sensitivity to RTK and PDGFR Inhibitors. Cancers, 14 (7), 1790. | |
dc.identifier.issn | 2072-6694 | es |
dc.identifier.uri | https://hdl.handle.net/11441/132204 | |
dc.description.abstract | High-grade glioma, including anaplastic astrocytoma and glioblastoma (GBM) patients, have a poor prognosis due to the lack of effective treatments. Therefore, the development of new therapeutic strategies to treat these gliomas is urgently required. Given that high-grade gliomas frequently harbor mutations in the SNF2 family chromatin remodeler ATRX, we performed a screen to identify FDA-approved drugs that are toxic to ATRX-deficient cells. Our findings reveal that multi-targeted receptor tyrosine kinase (RTK) and platelet-derived growth factor receptor (PDGFR) inhibitors cause higher cellular toxicity in high-grade glioma ATRX-deficient cells. Furthermore, we demonstrate that a combinatorial treatment of RTKi with temozolomide (TMZ)–the current standard of care treatment for GBM patients–causes pronounced toxicity in ATRX-deficient high-grade glioma cells. Our findings suggest that combinatorial treatments with TMZ and RTKi may increase the therapeutic window of opportunity in patients who suffer high-grade gliomas with ATRX mutations. Thus, we recommend incorporating the ATRX status into the analyses of clinical trials with RTKi and PDGFRi. | es |
dc.description.sponsorship | Danish National Research Foundation (DNRF115). | es |
dc.description.sponsorship | Danish Cancer Society (KBVU-2017_R167-A11063) | es |
dc.description.sponsorship | European Research Council (ERC-2015-STG679068) | es |
dc.description.sponsorship | Spanish Ministry of Science and Innovation (PID2020- 119329RB-I00) | es |
dc.format | application/pdf | es |
dc.format.extent | 17 p. | es |
dc.language.iso | eng | es |
dc.publisher | MDPI | es |
dc.relation.ispartof | Cancers, 14 (7), 1790. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | glioblastoma | es |
dc.subject | glioma | es |
dc.subject | ATRX | es |
dc.subject | drug screen | es |
dc.title | ATRX-Deficient High-Grade Glioma Cells Exhibit Increased Sensitivity to RTK and PDGFR Inhibitors | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.relation.projectID | (DNRF115) | es |
dc.relation.projectID | (KBVU-2017_R167-A11063) | es |
dc.relation.projectID | (PID2020- 119329RB-I00) | es |
dc.relation.projectID | (ERC-2015-STG679068) | es |
dc.relation.publisherversion | https://dx.doi.org/10.3390/cancers14071790 | es |
dc.identifier.doi | 10.3390/cancers14071790 | es |
dc.journaltitle | Cancers | es |
dc.publication.volumen | 14 | es |
dc.publication.issue | 7 | es |
dc.publication.endPage | 1790 | es |
dc.contributor.funder | Ministerio de Ciencia e Innovación (MICIN). España | es |
dc.contributor.funder | European Research Council (ERC) | es |
dc.contributor.funder | Danish Cancer Society | es |
dc.contributor.funder | Danish National Research Foundation | es |