ArticleInternational journal of molecular sciences2025
Combinatorial ERK Inhibition Enhances MAPK Pathway Suppression in BRAF-Mutant Melanoma.
Article in International journal of molecular sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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
4 citing papers in PubMed.
- Integrated Chemical, Computational, and Cellular Profiling of a Dual-Oil Melanoma Formulation: An Exploratory Life-Science Study.Life (Basel, Switzerland) · 2026Article
- Spatial biology of crowded tumor cells: A new map for designing drug combinations.Current opinion in structural biology · 2026Review
- Review
- BRAF inhibitor resistance in melanoma: from resistance mechanisms to therapeutic innovations.Molecular biomedicine · 2026Review
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Small molecule inhibitors targeting BRAF mutations at V600 and downstream MEK represent a significant advancement in treating BRAF-mutant melanoma. However, resistance mechanisms, often involving reactivation of the MAPK pathway via ERK1/2, limit their efficacy. The ERK1/2 inhibitor ravoxertinib (GDC0994) was tested on melanoma cell lines with and without resistance to BRAFi or BRAFi + MEKi. Short-term assays evaluated cell viability, apoptosis induction, and pathway modulation via Western Blot, while long-term effects were assessed using a colony formation assay. Resistant and parental melanoma cells responded to long-term ERKi treatment with reduced growth, independent of sensitivity to BRAF or MEK inhibitors. Adding ERKi to BRAFi/MEKi significantly enhanced apoptosis and growth inhibition, particularly in resistant lines. Although ravoxertinib alone showed limited antitumor activity, its combination with BRAFi/MEKi yielded substantial benefits, especially in chronic settings. These findings suggest that combinatorial regimens incorporating ERK inhibitors represent a promising therapeutic strategy for BRAF-mutant melanoma.
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Registered trials
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