ArticleNeoplasia (New York, N.Y.)2009
Growth-inhibitory and antiangiogenic activity of the MEK inhibitor PD0325901 in malignant melanoma with or without BRAF mutations.
Article in Neoplasia (New York, N.Y.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
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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.
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
65 citing papers in PubMed, 110 citations in OpenAlex.
- MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors.The Journal of clinical investigation · 2013Trial
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- ERK inhibits Capicua repressor function via multisite phosphorylation.Journal of cell science · 2026Article
- High-throughput drug screening identifies EGFR/MAPK pathway targeting sensitivities in organoid models of ovarian carcinosarcoma.Journal of experimental & clinical cancer research : CR · 2026Article
- MCLRP: enhanced prediction of anticancer drug response through low-rank matrix completion and transcriptomic profiling.BMC biology · 2025Article
- An Integrative Drug-Induced Transcriptomic Analysis Identifies Novel MYC Antagonists and Potential Synergistic Drug Combinations.Molecular carcinogenesis · 2025Article
- System analysis links SMARCD3 regulons to growth signaling and MEK inhibitor response in everolimus-resistant ER+ breast cancer cells.Cell reports. Medicine · 2025Article
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- Versatile Split-and-Mix Liposome PROTAC Platform for Efficient Degradation of Target ProteinJACS Au · 2024Article
- Phenotypic screening in Organ-on-a-Chip systems: a 1537 kinase inhibitor library screen on a 3D angiogenesis assay.Angiogenesis · 2024Article
- Strategies to inhibit FGFR4 V550L-driven rhabdomyosarcoma.British journal of cancer · 2022Article
- Interleukin-8 in Colorectal Cancer: A Systematic Review and Meta-Analysis of Its Potential Role as a Prognostic Biomarker.Biomedicines · 2022Article
- Mechanical Properties of the Extracellular Environment of Human Brain Cells Drive the Effectiveness of Drugs in Fighting Central Nervous System Cancers.Brain sciences · 2022Review
- SEMA6A/RhoA/YAP axis mediates tumor-stroma interactions and prevents response to dual BRAF/MEK inhibition in BRAF-mutant melanoma.Journal of experimental & clinical cancer research : CR · 2022Article
- Establishment of a novel method to assess MEK1/2 inhibition in PBMCs for clinical drug development.Frontiers in cell and developmental biology · 2022Article
- EGF-SNX3-EGFR axis drives tumor progression and metastasis in triple-negative breast cancers.Oncogene · 2022Article
- p38-MAPK-mediated translation regulation during early blastocyst development is required for primitive endoderm differentiation in mice.Communications biology · 2021Article
- TPL-2 kinase induces phagosome acidification to promote macrophage killing of bacteria.The EMBO journal · 2021Article
- MEK inhibitors for the treatment of non-small cell lung cancer.Journal of hematology & oncology · 2021Review
- Mechanistic Analysis of an Extracellular Signal-Regulated Kinase 2-Interacting Compound that Inhibits Mutant BRAF-Expressing Melanoma Cells by Inducing Oxidative Stress.The Journal of pharmacology and experimental therapeutics · 2021Article
5 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
16 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Raf/MEK/ERK pathway is an important mediator of tumor cell proliferation and angiogenesis. Here, we investigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC(50) in the nanomolar range even in the least responsive models. Growth inhibition was observed both in vitro and in vivo in xenograft models, regardless of BRAF mutation status, and was due to G(1)-phase cell cycle arrest and subsequent induction of apoptosis. Cell cycle (cyclin D1, c-Myc, and p27(KIP1)) and apoptosis (Bcl-2 and survivin) regulators were modulated by PD0325901 at the protein level. Gene expression profiling revealed profound modulation of several genes involved in the negative control of MAPK signaling and melanoma cell differentiation, suggesting alternative, potentially relevant mechanisms of action. Finally, PD0325901 inhibited the production of the proangiogenic factors vascular endothelial growth factor and interleukin 8 at a transcriptional level. In conclusion, PD0325901 exerts potent growth-inhibitory, proapoptotic, and antiangiogenic activity in melanoma lines, regardless of their BRAF mutation status. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective treatment strategies for patients experiencing malignant melanoma.
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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.