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dc.contributor.authorGirotti, MR
dc.contributor.authorLopes, F
dc.contributor.authorPreece, N
dc.contributor.authorNiculescu-Duvaz, D
dc.contributor.authorZambon, A
dc.contributor.authorDavies, L
dc.contributor.authorWhittaker, S
dc.contributor.authorSaturno, G
dc.contributor.authorViros, A
dc.contributor.authorPedersen, M
dc.contributor.authorSuijkerbuijk, BMJM
dc.contributor.authorMenard, D
dc.contributor.authorMcLeary, R
dc.contributor.authorJohnson, L
dc.contributor.authorFish, L
dc.contributor.authorEjiama, S
dc.contributor.authorSanchez-Laorden, B
dc.contributor.authorHohloch, J
dc.contributor.authorCarragher, N
dc.contributor.authorMacleod, K
dc.contributor.authorAshton, G
dc.contributor.authorMarusiak, AA
dc.contributor.authorFusi, A
dc.contributor.authorBrognard, J
dc.contributor.authorFrame, M
dc.contributor.authorLorigan, P
dc.contributor.authorMarais, R
dc.contributor.authorSpringer, C
dc.date.accessioned2020-08-05T12:53:43Z
dc.date.issued2015-01
dc.identifier.citationCancer cell, 2015, 27 (1), pp. 85 - 96
dc.identifier.issn1535-6108
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3905
dc.identifier.eissn1878-3686
dc.identifier.doi10.1016/j.ccell.2014.11.006
dc.description.abstractBRAF and MEK inhibitors are effective in BRAF mutant melanoma, but most patients eventually relapse with acquired resistance, and others present intrinsic resistance to these drugs. Resistance is often mediated by pathway reactivation through receptor tyrosine kinase (RTK)/SRC-family kinase (SFK) signaling or mutant NRAS, which drive paradoxical reactivation of the pathway. We describe pan-RAF inhibitors (CCT196969, CCT241161) that also inhibit SFKs. These compounds do not drive paradoxical pathway activation and inhibit MEK/ERK in BRAF and NRAS mutant melanoma. They inhibit melanoma cells and patient-derived xenografts that are resistant to BRAF and BRAF/MEK inhibitors. Thus, paradox-breaking pan-RAF inhibitors that also inhibit SFKs could provide first-line treatment for BRAF and NRAS mutant melanomas and second-line treatment for patients who develop resistance.
dc.formatPrint-Electronic
dc.format.extent85 - 96
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.subjectCell Line, Tumor
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectMice, Nude
dc.subjectMelanoma
dc.subjectMelanoma, Experimental
dc.subjectPhenylurea Compounds
dc.subjectPyrazines
dc.subjectProto-Oncogene Proteins B-raf
dc.subjectsrc-Family Kinases
dc.subjectAntineoplastic Agents
dc.subjectProtein Kinase Inhibitors
dc.subjectXenograft Model Antitumor Assays
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectDrug Resistance, Neoplasm
dc.subjectFemale
dc.titleParadox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma.
dc.typeJournal Article
dcterms.dateAccepted2014-11-07
rioxxterms.versionofrecord10.1016/j.ccell.2014.11.006
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2015-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer cell
pubs.issue1
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Gene & Oncogene Targeting
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Molecular Drug Resistance
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Gene & Oncogene Targeting
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Molecular Drug Resistance
pubs.publication-statusPublished
pubs.volume27
pubs.embargo.termsNot known
icr.researchteamGene & Oncogene Targetingen_US
icr.researchteamMolecular Drug Resistanceen_US
dc.contributor.icrauthorDavies, Lawrenceen
dc.contributor.icrauthorZambon, Alfonsoen
dc.contributor.icrauthorPreece, Natashaen
dc.contributor.icrauthorWhittaker, Stevenen
dc.contributor.icrauthorSpringer, Carolineen
dc.contributor.icrauthorNiculescu-Duvaz, Danen


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Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0