ArticleDisease models & mechanisms2012
Continual low-level MEK inhibition ameliorates cardio-facio-cutaneous phenotypes in zebrafish.
Article in Disease models & mechanisms, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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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.
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Who cites it
39 citing papers in PubMed, 61 citations in OpenAlex.
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- A Drug Discovery Pipeline for MAPK/ERK Pathway Inhibitors in Caenorhabditis elegans.Cancer research communications · 2024Article
- Exploring New Drug Repurposing Opportunities for MEK Inhibitors in RASopathies: A Comprehensive Review of Safety, Efficacy, and Future Perspectives of Trametinib and Selumetinib.Life (Basel, Switzerland) · 2024Review
- Non-Mammalian Models for Understanding Neurological Defects in RASopathies.Biomedicines · 2024Review
- Assessment of the FRET-based Teen sensor to monitor ERK activation changes preceding morphological defects in a RASopathy zebrafish model and phenotypic rescue by MEK inhibitor.Molecular medicine (Cambridge, Mass.) · 2024Article
- Abrogation of MAP4K4 protein function causes congenital anomalies in humans and zebrafish.Science advances · 2023Article
- Therapeutic targeting of vascular malformation in a zebrafish model of hereditary haemorrhagic telangiectasia.Disease models & mechanisms · 2023Article
- Nodal signaling establishes a competency window for stochastic cell fate switching.Developmental cell · 2022Article
- MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus.Neuro-oncology · 2022Review
- MEK-inhibitor-mediated rescue of skeletal myopathy caused by activating Hras mutation in a Costello syndrome mouse model.Disease models & mechanisms · 2022Article
- Zebrafish disease models in drug discovery: from preclinical modelling to clinical trials.Nature reviews. Drug discovery · 2021Review
- Matriptase activation of Gq drives epithelial disruption and inflammation via RSK and DUOX.eLife · 2021Article
- Modeling the developmental origins of pediatric cancer to improve patient outcomes.Disease models & mechanisms · 2021Review
- Gene dosage manipulation alleviates manifestations of hereditaryScience translational medicine · 2020Article
- The duality of human oncoproteins: drivers of cancer and congenital disorders.Nature reviews. Cancer · 2020Review
- Swimming toward solutions: Using fish and frogs as models for understanding RASopathies.Birth defects research · 2020Review
- Interference with ERK-dimerization at the nucleocytosolic interface targets pathological ERK1/2 signaling without cardiotoxic side-effects.Nature communications · 2020Article
- Entosis and apical cell extrusion constitute a tumor-suppressive mechanism downstream of Matriptase.The Journal of cell biology · 2020Article
- Rasopathies case report: concurrence of two pathogenic variations de novo in NF1 and KRAS genes in a patient.BMC pediatrics · 2019Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Cardio-facio-cutaneous (CFC) syndrome is caused by germline mutations in KRAS, BRAF and MEK1/2. The highly selective and potent MEK inhibitors that have been developed as anti-cancer agents hold potential as therapeutics for CFC syndrome. We have previously shown that the effects of CFC mutations on zebrafish gastrulation can be prevented by a 1-hour treatment with MEK inhibitors within a specific developmental time-window. However, MEK activity is essential for normal development and PD0325901 treatment outside this treatment window leads to additional developmental defects in MEK-dependent tissues. We now test ten different doses of PD0325901 at six developmental time points and assess the effects on body axis length, heart development and craniofacial structures in zebrafish embryos. Notably, we find that a continuous low-level dose of PD0325901 that has only minor inhibition of MEK activity can prevent the action of both the common CFC BRAF(Q257R) kinase-active allele and the BRAF(G596V) kinase-impaired mutant allele through the first 5 days of development. These results provide a detailed study of the effects of PD0325901 in development and show that, unlike in cancer, which requires robust inhibition of MAPK signalling, a partial reduction in phospho-ERK1/2 activity is sufficient to moderate the developmental effects of BRAF(CFC) mutations.
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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.