ArticleeLife2013
BRAF inhibitors suppress apoptosis through off-target inhibition of JNK signaling.
Article in eLife, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 51 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 80 citations in OpenAlex.
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- Polyamine Metabolism and the DHPS/eIF5A Hypusination Axis: From Metabolic Reprogramming to a Therapeutic Achilles' Heel in Melanoma.Biomolecules · 2026Review
- Vemurafenib Induces Apoptosis via JNK Activation and AKT Inhibition in Hepatocellular Carcinoma.Journal of Cancer · 2026Article
- Increased Mitochondrial Superoxide Level Is Partially Associated With Vemurafenib-Induced Renal Tubular Toxicity.Basic & clinical pharmacology & toxicology · 2025Article
- The paradoxical activity of BRAF inhibitors: potential use in wound healing.Archives of dermatological research · 2025Review
- BRAF Modulates the Interplay Between Cell-Cell and Cell-Extracellular Matrix Adhesions in PECAM-1-Mediated Mechanotransduction.International journal of molecular sciences · 2024Article
- Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells.Cell reports · 2024Article
- Targeting PEAK1 sensitizes anaplastic thyroid carcinoma cells harboring BRAFHistology and histopathology · 2024Article
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- The evolution of BRAF-targeted therapies in melanoma: overcoming hurdles and unleashing novel strategies.Frontiers in oncology · 2024Review
- OncogenicNeural regeneration research · 2023Article
- Vemurafenib improves muscle histopathology in a mouse model of LAMA2-related congenital muscular dystrophy.Disease models & mechanisms · 2023Article
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- Ribosome impairment regulates intestinal stem cell identity via ZAKɑ activation.Nature communications · 2022Article
- miR-181a Promotes Multiple Protumorigenic Functions by Targeting TGFβR3.The Journal of investigative dermatology · 2022Article
- Identification and validation of four photodynamic therapy related genes inhibiting MAPK and inducing cell cycle alteration in squamous cell carcinoma.Frontiers in oncology · 2022Article
- Identification of a dual TAOK1 and MAP4K5 inhibitor using a structure-based virtual screening approach.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- The Performance of HepG2 and HepaRG Systems through the Glass of Acetaminophen-Induced Toxicity.Life (Basel, Switzerland) · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
25 authors at 4 institutions in 2 countries.
Funding
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 through the inhibition of multiple off-target kinases upstream of c-Jun N-terminal kinase (JNK), principally ZAK. JNK signaling is suppressed in multiple contexts, including in cSCC of vemurafenib-treated patients, as well as in mice. Expression of a mutant ZAK that cannot be inhibited reverses the suppression of JNK activation and apoptosis. Our results implicate suppression of JNK-dependent apoptosis as a significant, independent mechanism that cooperates with paradoxical ERK activation to induce cSCC, suggesting broad implications for understanding toxicities associated with BRAF inhibitors and for their use in combination therapies. DOI: http://dx.doi.org/10.7554/eLife.00969.001.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.