2013
DOI: 10.7554/elife.00969
|View full text |Cite
|
Sign up to set email alerts
|

Abstract: Vemurafenib and dabrafenib selectively inhibit the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) kinase, resulting in high response rates and increased survival in melanoma. Approximately 22% of individuals treated with vemurafenib develop cutaneous squamous cell carcinoma (cSCC) during therapy. The prevailing explanation for this is drug-induced paradoxical ERK activation, resulting in hyperproliferation. Here we show an unexpected and novel effect of vemurafenib/PLX4720 in suppressing apoptosis throu… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
1
1
1
1

Citation Types

4
88
0

Year Published

2014
2014
2022
2022

Publication Types

Select...
7
2
1

Relationship

0
10

Authors

Journals

citations
Cited by 69 publications
(92 citation statements)
references
References 68 publications
4
88
0
Order By: Relevance
“…The commonly used noncompetitive inhibitors of the GTPase activity of dynamin, dynasore and its close structural analog Dyngo-4A, were shown to produce the inhibitory effect on fluid-phase endocytosis in dynamin triple knock-out cells (Park et al, 2013). The multiple off-targets of BCR-ABL, BRAF, VEGFR, JAK2, and PARP inhibitors were also recently documented (Antolín and Mestres, 2014; Green et al, 2013;Kitagawa et al, 2013;Steegmann et al, 2012;Vin et al, 2013).…”
Section: Discussionmentioning
confidence: 91%
“…The commonly used noncompetitive inhibitors of the GTPase activity of dynamin, dynasore and its close structural analog Dyngo-4A, were shown to produce the inhibitory effect on fluid-phase endocytosis in dynamin triple knock-out cells (Park et al, 2013). The multiple off-targets of BCR-ABL, BRAF, VEGFR, JAK2, and PARP inhibitors were also recently documented (Antolín and Mestres, 2014; Green et al, 2013;Kitagawa et al, 2013;Steegmann et al, 2012;Vin et al, 2013).…”
Section: Discussionmentioning
confidence: 91%
“…This may be important in the context of a recent report indicating that BRAF inhibitor-driven tumor proliferation in a KRASmutated colon carcinoma could not be overcome by MEK1/2 inhibition (31). The differences between the 2 BRAF inhibitors vemurafenib and dabrafenib are another clinically relevant aspect, as, for example, off-target effects of vemurafenib, such as cutaneous squamous cell carcinoma, which were less frequently observed with dabrafenib (32). Cutaneous squamous cell carcinoma rates were reported to be between 20% and 26% in trials with vemurafenib (1,33), while the rates were 6% to 11% in dabrafenib trials (34)(35)(36)(37).…”
Section: Methodsmentioning
confidence: 99%
“…In contrast to the ERK pathway, which primarily promotes cellular proliferation, JNK and p38 phosphorylate a range of substrates to promote inflammation and cell death (1,3). In addition, cross-regulation among the p38, JNK, and ERK pathways is important for the efficacy of various cancer therapies that are in use or in development (4,5). Molecular details on the more diverse upstream regulation of the p38 and JNK pathways are currently less clear, however.…”
mentioning
confidence: 99%