ArticleThe Journal of investigative dermatology2015
Combined Inhibition of MEK and Plk1 Has Synergistic Antitumor Activity in NRAS Mutant Melanoma.
Article in The Journal of investigative dermatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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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
41 citing papers in PubMed, 63 citations in OpenAlex.
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- A Novel Solution-Blow-Spinning Device Cosprays Autologous Skin Cell Suspensions and Polymer in the Treatment of Full Thickness Wounds in a Murine Model.The Journal of surgical research · 2025Article
- The cell cycle regulator PLK1 promotes murine melanoma progression by regulating the transcription factor BACH1.PLoS biology · 2025Article
- Mitochondrial signatures shape phenotype switching and apoptosis in response to PLK1 inhibitors.Life science alliance · 2025Article
- PLK1 in cancer therapy: a comprehensive review of immunomodulatory mechanisms and therapeutic opportunities.Frontiers in immunology · 2025Review
- Predicting anti-cancer drug combination responses with a temporal cell state network model.PLoS computational biology · 2023Article
- A Drosophila chemical screen reveals synergistic effect of MEK and DGKα inhibition in Ras-driven cancer.Disease models & mechanisms · 2023Article
- Resistance to BRAF Inhibitors: EZH2 and Its Downstream Targets as Potential Therapeutic Options in Melanoma.International journal of molecular sciences · 2023Article
- Piperine-Chlorogenic Acid Hybrid Inhibits the Proliferation of the SK-MEL-147 Melanoma Cells by Modulating Mitotic Kinases.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Melanogenesis and the Targeted Therapy of Melanoma.Biomolecules · 2022Review
- A Genome-Wide Screen Identifies PDPK1 as a Target to Enhance the Efficacy of MEK1/2 Inhibitors in NRAS Mutant Melanoma.Cancer research · 2022Article
- Employing CRISPR-Cas9 to Generate CD133 Synthetic Lethal Melanoma Stem Cells.International journal of molecular sciences · 2022Article
- PLK1 inhibition-based combination therapies for cancer management.Translational oncology · 2022Review
- Article
- Present and Future Perspective on PLK1 Inhibition in Cancer Treatment.Frontiers in oncology · 2022Review
- Nanotechnology Addressing Cutaneous Melanoma: The Italian Landscape.Pharmaceutics · 2021Review
- Management and Outcomes of Blast Transformed Chronic Myelomonocytic Leukemia.Current hematologic malignancy reports · 2021Review
- Fibroblasts Influence Metastatic Melanoma Cell Sensitivity to Combined BRAF and MEK Inhibition.Cancers · 2021Article
- Review
- Assessment of RAS Dependency for BRAF Alterations Using Cancer Genomic Databases.JAMA network open · 2021Article
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
Abstract
About one-third of cancers harbor activating mutations in rat sarcoma viral oncogene homolog (RAS) oncogenes. In melanoma, aberrant neuroblastoma-RAS (NRAS) signaling fuels tumor progression in about 20% of patients. Current therapeutics for NRAS-driven malignancies barely affect overall survival. To date, pathway interference downstream of mutant NRAS seems to be the most promising approach. In this study, data revealed that mutant NRAS induced Polo-like kinase 1 (Plk1) expression, and pharmacologic inhibition of Plk1 stabilized the size of NRAS mutant melanoma xenografts. The combination of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK) and Plk1 inhibitors resulted in a significant growth reduction of NRAS mutant melanoma cells in vitro, and regression of xenografted NRAS mutant melanoma in vivo. Independent cell cycle arrest and increased induction of apoptosis underlies the synergistic effect of this combination. Data further suggest that the p53 signaling pathway is of key importance to the observed therapeutic efficacy. This study provides in vitro, in vivo, and first mechanistic data that an MEK/Plk1 inhibitor combination might be a promising treatment approach for patients with NRAS-driven melanoma. As mutant NRAS signaling is similar across different malignancies, this inhibitor combination could also offer a previously unreported treatment modality for NRAS mutant tumors of other cell origins.
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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.