dc.contributor.author | Girotti, MR | |
dc.contributor.author | Lopes, F | |
dc.contributor.author | Preece, N | |
dc.contributor.author | Niculescu-Duvaz, D | |
dc.contributor.author | Zambon, A | |
dc.contributor.author | Davies, L | |
dc.contributor.author | Whittaker, S | |
dc.contributor.author | Saturno, G | |
dc.contributor.author | Viros, A | |
dc.contributor.author | Pedersen, M | |
dc.contributor.author | Suijkerbuijk, BMJM | |
dc.contributor.author | Menard, D | |
dc.contributor.author | McLeary, R | |
dc.contributor.author | Johnson, L | |
dc.contributor.author | Fish, L | |
dc.contributor.author | Ejiama, S | |
dc.contributor.author | Sanchez-Laorden, B | |
dc.contributor.author | Hohloch, J | |
dc.contributor.author | Carragher, N | |
dc.contributor.author | Macleod, K | |
dc.contributor.author | Ashton, G | |
dc.contributor.author | Marusiak, AA | |
dc.contributor.author | Fusi, A | |
dc.contributor.author | Brognard, J | |
dc.contributor.author | Frame, M | |
dc.contributor.author | Lorigan, P | |
dc.contributor.author | Marais, R | |
dc.contributor.author | Springer, C | |
dc.date.accessioned | 2020-08-05T12:53:43Z | |
dc.date.issued | 2015-01-12 | |
dc.identifier.citation | Cancer cell, 2015, 27 (1), pp. 85 - 96 | |
dc.identifier.issn | 1535-6108 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3905 | |
dc.identifier.eissn | 1878-3686 | |
dc.identifier.doi | 10.1016/j.ccell.2014.11.006 | |
dc.description.abstract | BRAF 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.format | Print-Electronic | |
dc.format.extent | 85 - 96 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Mice, Nude | |
dc.subject | Melanoma | |
dc.subject | Melanoma, Experimental | |
dc.subject | Phenylurea Compounds | |
dc.subject | Pyrazines | |
dc.subject | Proto-Oncogene Proteins B-raf | |
dc.subject | src-Family Kinases | |
dc.subject | Antineoplastic Agents | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Xenograft Model Antitumor Assays | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Female | |
dc.title | Paradox-breaking RAF inhibitors that also target SRC are effective in drug-resistant BRAF mutant melanoma. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2014-11-07 | |
rioxxterms.versionofrecord | 10.1016/j.ccell.2014.11.006 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2015-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cancer cell | |
pubs.issue | 1 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 27 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Gene & Oncogene Targeting | |
icr.researchteam | Molecular Drug Resistance | |
dc.contributor.icrauthor | Preece, Natasha | |
dc.contributor.icrauthor | Zambon, Alfonso | |
dc.contributor.icrauthor | Davies, Lawrence | |
dc.contributor.icrauthor | Whittaker, Steven | |
dc.contributor.icrauthor | Springer, Caroline | |