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Dangerous liaisons: flirtations between oncogenic BRAF and GRP78 in drug-resistant melanomas.

dc.contributor.author Shenolikar, Shirish
dc.date.accessioned 2018-07-16T17:07:46Z
dc.date.available 2018-07-16T17:07:46Z
dc.date.issued 2014-03
dc.identifier 74609
dc.identifier.issn 0021-9738
dc.identifier.issn 1558-8238
dc.identifier.uri https://hdl.handle.net/10161/17237
dc.description.abstract BRAF mutations in aggressive melanomas result in kinase activation. BRAF inhibitors reduce BRAF(V600E) tumors, but rapid resistance follows. In this issue of the JCI, Ma and colleagues report that vemurafenib activates ER stress and autophagy in BRAF(V600E) melanoma cells, through sequestration of the ER chaperone GRP78 by the mutant BRAF and subsequent PERK activation. In preclinical studies, treating vemurafenib-resistant melanoma with a combination of vemurafenib and an autophagy inhibitor reduced tumor load. Further work is needed to establish clinical relevance of this resistance mechanism and demonstrate efficacy of autophagy and kinase inhibitor combinations in melanoma treatment.
dc.language eng
dc.publisher AMER SOC CLINICAL INVESTIGATION INC
dc.relation.ispartof The Journal of clinical investigation
dc.relation.isversionof 10.1172/jci74609
dc.subject Animals
dc.subject Humans
dc.subject Melanoma
dc.subject Sulfonamides
dc.subject Indoles
dc.subject Proto-Oncogene Proteins B-raf
dc.subject Antineoplastic Agents
dc.subject Autophagy
dc.subject Endoplasmic Reticulum Stress
dc.title Dangerous liaisons: flirtations between oncogenic BRAF and GRP78 in drug-resistant melanomas.
dc.type Journal article
dc.date.updated 2018-07-16T17:07:44Z
pubs.begin-page 973
pubs.end-page 976
pubs.issue 3
pubs.organisational-group School of Medicine
pubs.organisational-group Duke
pubs.organisational-group Psychiatry & Behavioral Sciences, Translational Neuroscience
pubs.organisational-group Psychiatry & Behavioral Sciences
pubs.organisational-group Clinical Science Departments
pubs.publication-status Published
pubs.volume 124
duke.contributor.orcid Shenolikar, Shirish|0000-0003-0540-6328


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