ArticleInternational journal of molecular sciences2019
Effective Treatment of Metastatic Melanoma by Combining MAPK and PI3K Signaling Pathway Inhibitors.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed.
- Acquired BRAFi Resistance Increases Melanoma Cell Sensitivity to Metabolic Targeting with Metformin.International journal of molecular sciences · 2026Article
- Macrophage efferocytosis mediated by the TP63-RAC2 pathway promotes immunosuppressive remodeling in esophageal cancer.Cell reports. Medicine · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- AI-Guided Discovery of Oncogenic Signaling Crosstalk in Tumor Progression and Drug Resistance.Oncology research · 2026Review
- Article
- Cancer drug sensitivity estimation using modular deep Graph Neural Networks.NAR genomics and bioinformatics · 2024Article
- Comparative Analysis of Olive-Derived Phenolic Compounds' Pro-Melanogenesis Effects on B16F10 Cells and Epidermal Human Melanocytes.International journal of molecular sciences · 2024Article
- Review
- Disrupting cellular memory to overcome drug resistance.Nature communications · 2023Article
- PI3K/AKT signaling allows for MAPK/ERK pathway independency mediating dedifferentiation-driven treatment resistance in melanoma.Cell communication and signaling : CCS · 2022Article
- The future of targeted kinase inhibitors in melanoma.Pharmacology & therapeutics · 2022Review
- Selected Flavonoids to Target Melanoma: A Perspective in Nanoengineering Delivery Systems.Bioengineering (Basel, Switzerland) · 2022Review
- CRISPR/Cas9 Mediated Knockout of Cyclooxygenase-2 Gene Inhibits Invasiveness in A2058 Melanoma Cells.Cells · 2022Article
- CCT196969 effectively inhibits growth and survival of melanoma brain metastasis cells.PloS one · 2022Article
- The NF-κB pathway is critically implicated in the oncogenic phenotype of human osteosarcoma cells.Journal of applied biomedicine · 2021Article
- HOXC10 promotes growth and migration of melanoma by regulating Slug to activate the YAP/TAZ signaling pathway.Discover oncology · 2021Article
- RTK Inhibitors in Melanoma: From Bench to Bedside.Cancers · 2021Review
- Research update on the anticancer effects of buparlisib.Oncology letters · 2021Review
- Potent and Selective Mitogen-Activated Protein Kinase Kinase 1/2 (MEK1/2) Heterobifunctional Small-molecule Degraders.Journal of medicinal chemistry · 2020Article
- The Role of BRAF in Metastatic Colorectal Carcinoma-Past, Present, and Future.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Malignant melanoma is the most aggressive type of skin cancer and is closely associated with the development of brain metastases. Despite aggressive treatment, the prognosis has traditionally been poor, necessitating improved therapies. In melanoma, the mitogen activated protein kinase and the phosphoinositide 3-kinase signaling pathways are commonly altered, and therapeutically inhibiting one of the pathways often upregulates the other, leading to resistance. Thus, combined treatment targeting both pathways is a promising strategy to overcome this. Here, we studied the in vitro and in vivo effects of the PI3K inhibitor buparlisib and the MEK1/2 inhibitor trametinib, used either as targeted monotherapies or in combination, on patient-derived melanoma brain metastasis cell lines. Scratch wound and trans-well assays were carried out to assess the migratory capacity of the cells upon drug treatment, whereas flow cytometry, apoptosis array and Western blots were used to study apoptosis. Finally, an in vivo treatment experiment was carried out on NOD/SCID mice. We show that combined therapy was more effective than monotherapy. Combined treatment also more effectively increased apoptosis, and inhibited tumor growth in vivo. This suggests a clinical potential of combined treatment to overcome ceased treatment activity which is often seen after monotherapies, and strongly encourages the evaluation of the treatment strategy on melanoma patients with brain metastases.
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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.