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dc.contributor.authorCarmell, N.
dc.contributor.authorRominiyi, O.
dc.contributor.authorMyers, K.N.
dc.contributor.authorMcGarrity-Cottrell, C.
dc.contributor.authorVanderlinden, A.
dc.contributor.authorLad, N.
dc.contributor.authorPerroux-David, E.
dc.contributor.authorEl-Khamisy, Sherif
dc.contributor.authorFernando, M.
dc.contributor.authorFinegan, K.G.
dc.contributor.authorBrown, S.
dc.contributor.authorCollis, S.J.
dc.date.accessioned2023-11-01T15:21:24Z
dc.date.accessioned2023-11-10T13:38:33Z
dc.date.available2023-11-01T15:21:24Z
dc.date.available2023-11-10T13:38:33Z
dc.date.issued2021-03
dc.identifier.citationCarmell N, Rominiyi O, Myers KN et al (2021) Identification and Validation of ERK5 as a DNA Damage Modulating Drug Target in Glioblastoma. Cancers. 13(5): 944.
dc.identifier.urihttp://hdl.handle.net/10454/19671
dc.descriptionYes
dc.description.abstractBrain tumours kill more children and adults under 40 than any other cancer, with approximately half of primary brain tumours being diagnosed as high-grade malignancies known as glioblastomas. Despite de-bulking surgery combined with chemo-/radiotherapy regimens, the mean survival for these patients is only around 15 months, with less than 10% surviving over 5 years. This dismal prognosis highlights the urgent need to develop novel agents to improve the treatment of these tumours. To address this need, we carried out a human kinome siRNA screen to identify potential drug targets that augment the effectiveness of temozolomide (TMZ)-the standard-of-care chemotherapeutic agent used to treat glioblastoma. From this we identified ERK5/MAPK7, which we subsequently validated using a range of siRNA and small molecule inhibitors within a panel of glioma cells. Mechanistically, we find that ERK5 promotes efficient repair of TMZ-induced DNA lesions to confer cell survival and clonogenic capacity. Finally, using several glioblastoma patient cohorts we provide target validation data for ERK5 as a novel drug target, revealing that heightened ERK5 expression at both the mRNA and protein level is associated with increased tumour grade and poorer patient survival. Collectively, these findings provide a foundation to develop clinically effective ERK5 targeting strategies in glioblastomas and establish much-needed enhancement of the therapeutic repertoire used to treat this currently incurable disease.
dc.language.isoen
dc.rights(c) 2021 The Authors. This is an Open Access article distributed under the Creative Commons CC-BY license ()
dc.subjectERK5
dc.subjectMAPK7
dc.subjectGlioblastoma
dc.subjectTemozolomide
dc.subjectDNA damage
dc.subjectSensitisation
dc.titleIdentification and Validation of ERK5 as a DNA Damage Modulating Drug Target in Glioblastoma
dc.status.refereedYes
dc.date.Accepted2021-02-22
dc.date.application2021-02-24
dc.typeArticle
dc.type.versionPublished version
dc.identifier.doihttps://doi.org/10.3390%2Fcancers13050944
dc.rights.licenseCC-BY
dc.date.updated2023-11-01T15:21:25Z
refterms.dateFOA2023-11-10T13:38:54Z
dc.openaccess.statusopenAccess


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