Trial reportBritish journal of cancer2020
Dual-specificity protein phosphatase DUSP4 regulates response to MEK inhibition in BRAF wild-type melanoma.
Trial report in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Effect of prior and first-line immunotherapy on baseline immune biomarkers and modulation of the tumor microenvironment in response to nivolumab and relatlimab combination therapy in patients with melanoma from RELATIVITY-020.Journal for immunotherapy of cancer · 2025Trial
- DUSP4 promotes anti-tumor CD8Nature communications · 2026Article
- Ubiquitin-mediated stabilization of KDM5B drives chemoresistance via repression of dual-specificity phosphatase 4 in ovarian cancer.Signal transduction and targeted therapy · 2026Article
- Distinct molecular subtypes of KRASClinical and translational medicine · 2025Article
- Discovery of KRAS(G12D) selective degrader ASP3082.Communications chemistry · 2025Article
- STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20-Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- The transcription factor PITX1 cooperates with super-enhancers to regulate the expression of DUSP4 and inhibit pyroptosis in pulmonary artery smooth muscle cells.Respiratory research · 2025Article
- Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies.Signal transduction and targeted therapy · 2024Review
- Diurnal gene expression patterns in retina and choroid distinguish myopia progression from myopia onset.PloS one · 2024Article
- CRISPR screens identify gene targets at breast cancer risk loci.Genome biology · 2023Article
- Mitogen-Activated Protein Kinase Phosphatases: No Longer Undruggable?Annual review of pharmacology and toxicology · 2023Review
- Investigating the Role of DUSP4 in Uveal Melanoma.Translational vision science & technology · 2022Article
- Regulation of TORC1 by MAPK Signaling Determines Sensitivity and Acquired Resistance to Trametinib in Pediatric BRAFV600E Brain Tumor Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Article
- Dual-specificity phosphatases: therapeutic targets in cancer therapy resistance.Journal of cancer research and clinical oncology · 2022Review
- Loss of DUSP4 Expression as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma.Diagnostics (Basel, Switzerland) · 2021Article
- Circular RNA hsa_circ_0001666 sponges miR‑330‑5p, miR‑193a‑5p and miR‑326, and promotes papillary thyroid carcinoma progression via upregulation of ETV4.Oncology reports · 2021Article
- Review
- Analysis of CRISPR-Cas9 screens identifies genetic dependencies in melanoma.Pigment cell & melanoma research · 2021Article
- Article
- Function and regulation of the PEA3 subfamily of ETS transcription factors in cancer.American journal of cancer research · 2020Review
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundAiming to improve treatment options for BRAF wild-type melanoma, we previously conducted the DOC-MEK study of docetaxel with MEK inhibitor (MEKi) selumetinib or placebo, revealing trends to prolongation of progression-free survival (hazard ratio 0.75, P = 0.130), and improved response rates (32% vs 14%, P = 0.059) with docetaxel plus selumetinib. NRAS status did not associate with outcome. Here, the aim was to identify novel biomarkers of response to MEKi.
methodsA MEK 6 gene signature was quantified using NanoString and correlated with clinical outcomes. Two components of the gene signature were investigated by gene silencing in BRAF/NRAS wild-type melanoma cells.
resultsIn melanomas of patients on the selumetinib but not the placebo arm, two gene signature components, dual-specificity protein phosphatase 4 (DUSP4) and ETS translocation variant 4 (ETV4), were expressed more highly in responders than non-responders. In vitro, ETV4 depletion inhibited cell survival but did not influence sensitivity to MEKi selumetinib or trametinib. In contrast, DUSP4-depleted cells showed enhanced cell survival and increased resistance to both selumetinib and trametinib.
conclusionsETV4 and DUSP4 associated with clinical response to docetaxel plus selumetinib. DUSP4 depletion induced MEKi resistance, suggesting that DUSP4 is not only a biomarker but also a mediator of MEKi sensitivity. CLINICAL
trial registrationDOC-MEK (EudraCT no: 2009-018153-23).
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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.