ArticleCell research2018
MAP3K1 and MAP2K4 mutations are associated with sensitivity to MEK inhibitors in multiple cancer models.
Article in Cell research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- Applications of lung cancer organoids in precision medicine: from bench to bedside.Cell communication and signaling : CCS · 2023Pooled it
- Nivolumab adjuvant to chemo-radiation in localized muscle-invasive urothelial cancer: primary analysis of a multicenter, single-arm, phase II, investigator-initiated trial (NEXT).Journal for immunotherapy of cancer · 2025Trial
- Article
- MAP3K1: A Multifunctional Kinase at the Crossroads of Cancer Progression and Tumor Suppression.Cells · 2026Review
- Mutational Signatures and Clonal Hematopoiesis in Intestinal Metaplasia across Countries with Varying Stomach Cancer Incidence.Cancer discovery · 2026Article
- CRISPR knockout screens reveal JUN as the master mediator of resistance to MAPK inhibition in KRAS-mutant pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Unravelling Resistance: Integrating Metabolism, Epigenetics, Immunology, and Proteostasis in Strategies against Kirsten Rat Sarcoma Viral Oncogene Homolog-mutant Colorectal Cancer.International journal of biological sciences · 2026Review
- Article
- Tumor necrosis associates with aggressive breast cancer features, increased hypoxia signaling and reduced patient survival.Scientific reports · 2025Article
- Actionable Genes and Carcinogenic Pathways for Gastric Cancer in Latinos.Cancer medicine · 2025Article
- CARM1-Mediated MAP2K4 Methylation Potentiates the Oncogenic Functions of MAP2K4 and Constitutes a Targetable Dependency in Triple-Negative Breast Cancer.Cancer research · 2025Article
- Molecular and functional profiling unravels targetable vulnerabilities in colorectal cancer.Molecular oncology · 2025Article
- Spike-in enhanced phosphoproteomics uncovers synergistic signaling responses to MEK inhibition in colon cancer cells.Nature communications · 2025Article
- A Selective MAP3K1 Inhibitor Facilitates Discovery of NPM1 as a Member of the Network.Molecules (Basel, Switzerland) · 2025Article
- Mutation impact on mRNA versus protein expression across human cancers.GigaScience · 2025Article
- Synthetic lethal strategies for the development of cancer therapeutics.Nature reviews. Clinical oncology · 2025Review
- PARP Pioneers: Using BRCA1/2 Mutation-targeted Inhibition to Revolutionize Breast Cancer Treatment.Current pharmaceutical design · 2025Review
- The impact of targeted therapies on molecular alterations identified by an institutional molecular tumor board: an approach based on ESCAT classification.ESMO real world data and digital oncology · 2024Article
- Dual-Specificity Phosphatase 4 Promotes Malignant Features in Colorectal Cancer Through Cyclic-AMP Response Element Binding Protein/Protein Kinase CAMP-Activated Catalytic Subunit Beta Activation.Digestive diseases and sciences · 2024Article
- Small-molecule inhibition of MAP2K4 is synergistic with RAS inhibitors inProceedings of the National Academy of Sciences of the United States of America · 2024Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Activation of the mitogen-activated protein kinase (MAPK) pathway is frequent in cancer. Drug development efforts have been focused on kinases in this pathway, most notably on RAF and MEK. We show here that MEK inhibition activates JNK-JUN signaling through suppression of DUSP4, leading to activation of HER Receptor Tyrosine Kinases. This stimulates the MAPK pathway in the presence of drug, thereby blunting the effect of MEK inhibition. Cancers that have lost MAP3K1 or MAP2K4 fail to activate JNK-JUN. Consequently, loss-of-function mutations in either MAP3K1 or MAP2K4 confer sensitivity to MEK inhibition by disabling JNK-JUN-mediated feedback loop upon MEK inhibition. In a panel of 168 Patient Derived Xenograft (PDX) tumors, MAP3K1 and MAP2K4 mutation status is a strong predictor of response to MEK inhibition. Our findings suggest that cancers having mutations in MAP3K1 or MAP2K4, which are frequent in tumors of breast, prostate and colon, may respond to MEK inhibitors. Our findings also suggest that MAP3K1 and MAP2K4 are potential drug targets in combination with MEK inhibitors, in spite of the fact that they are encoded by tumor suppressor genes.
Indexed as
Identifiers
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.