ArticleOncotarget2017
Human melanoma cells resistant to MAPK inhibitors can be effectively targeted by inhibition of the p90 ribosomal S6 kinase.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 48 citations in OpenAlex.
- Targeting the MAPK Pathway in Cancer.International journal of molecular sciences · 2025Review
- Combinatorial ERK Inhibition Enhances MAPK Pathway Suppression in BRAF-Mutant Melanoma.International journal of molecular sciences · 2025Article
- Mitochondrial signatures shape phenotype switching and apoptosis in response to PLK1 inhibitors.Life science alliance · 2025Article
- Targeting RSK2 in Cancer Therapy: A Review of Natural Products.Anti-cancer agents in medicinal chemistry · 2025Review
- Early host immune responses in a human organoid-derived gallbladder monolayer toFrontiers in immunology · 2024Article
- YB-1 activating cascades as potential targets in KRAS-mutated tumors.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2023Review
- Inhibition of p90 ribosomal S6 kinases disrupts melanoma cell growth and immune evasion.Journal of experimental & clinical cancer research : CR · 2023Article
- Scaffolding Protein Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) Regulates MAPK Inhibition Responsiveness in Pancreas Cancer via Crosstalk with AKT Signaling.Molecular cancer research : MCR · 2023Article
- Biomechanical and biochemical assessment of YB-1 expression in A375 melanoma cell line: Exploratory study.Frontiers in molecular medicine · 2023Article
- RSK2 promotes melanoma cell proliferation and vemurafenib resistanceFrontiers in pharmacology · 2022Article
- Article
- Identifying requirements for RSK2 specific inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- A comprehensive review of the functions of YB-1 in cancer stemness, metastasis and drug resistance.Cellular signalling · 2021Review
- Review
- Blocking Y-Box Binding Protein-1 through Simultaneous Targeting of PI3K and MAPK in Triple Negative Breast Cancers.Cancers · 2020Article
- Tumour Progression Stage-Dependent Secretion of YB-1 Stimulates Melanoma Cell Migration and Invasion.Cancers · 2020Article
- Aberrant modulation of ribosomal protein S6 phosphorylation confers acquired resistance to MAPK pathway inhibitors in BRAF-mutant melanoma.Acta pharmacologica Sinica · 2019Article
- Reversal of Resistance in Targeted Therapy of Metastatic Melanoma: Lessons Learned from Vemurafenib (BRAFCancers · 2018Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinical availability of small molecule inhibitors specifically targeting mutated BRAF marked a significant breakthrough in melanoma therapy. Despite a dramatic anti-tumour activity and improved patient survival, rapidly emerging resistance, however, greatly limits the clinical benefit. The majority of the already described resistance mechanisms involve a reactivation of the MAPK signalling pathway. The p90 ribosomal S6 kinase (RSK), a downstream effector of the MAPK signalling cascade, has been reported to enhance survival of melanoma cells in response to chemotherapy. Here, we can show that RSK activity is significantly increased in human melanoma cells with acquired resistance to the BRAFV600E/K inhibitor vemurafenib. Interestingly, inhibition of RSK signalling markedly impairs the viability of vemurafenib resistant melanoma cells and is effective both in two-dimensional and in three-dimensional culture systems, especially in a chronic, long-term application. The effect of RSK inhibition can be partly replicated by downregulation of the well-known RSK target, Y-box binding protein 1 (YB-1). Intriguingly, RSK inhibition also retains its efficacy in melanoma cells with combined resistance to vemurafenib and the MEK inhibitor trametinib. These data suggest that active RSK signalling might be an attractive novel therapeutic target in melanoma with acquired resistance to MAPK pathway inhibitors.
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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.