ArticleInternational journal of oncology2015
Kinase inhibitor screening identifies CDK4 as a potential therapeutic target for melanoma.
Article in International journal of oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Roles and mechanisms of aberrant alternative splicing in melanoma - implications for targeted therapy and immunotherapy resistance.Cancer cell international · 2024Review
- Marine-Derived Bisindoles for Potent Selective Cancer Drug Discovery and Development.Molecules (Basel, Switzerland) · 2024Review
- A New Mild Method for Synthesis of Marine Alkaloid Fascaplysin and Its Therapeutically Promising Derivatives.Marine drugs · 2023Article
- Marine-Derived Lead Fascaplysin: Pharmacological Activity, Total Synthesis, and Structural Modification.Marine drugs · 2023Review
- Comparison of the Inhibitory Binding Modes Between the Planar Fascaplysin and Its Nonplanar Tetrahydro-β-carboline Analogs in CDK4.Frontiers in chemistry · 2021Article
- Basic Pan-Cancer Analysis of the Carcinogenic Effects of Cyclin-Dependent Kinase 4 (CDK4) in Human Surface Tumors.Journal of healthcare engineering · 2021Article
- Jumonji domain-containing protein 6 protein and its role in cancer.Cell proliferation · 2020Review
- Combined targeting EGFR and SRC as a potential novel therapeutic approach for the treatment of triple negative breast cancer.Therapeutic advances in medical oncology · 2020Article
- Regulation of PRMT5-MDM4 axis is critical in the response to CDK4/6 inhibitors in melanoma.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Profiling of prognostic alternative splicing in melanoma.Oncology letters · 2019Article
- The interplay of CDK4 and CDK6 in melanoma.Oncotarget · 2019Article
- The Melding of Drug Screening Platforms for Melanoma.Frontiers in oncology · 2019Review
- Fascaplysin Sensitizes Anti-Cancer Effects of Drugs Targeting AKT and AMPK.Molecules (Basel, Switzerland) · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite recent advances in targeted therapies and immunotherapies metastatic melanoma remains only rarely curable. The objective of the present study was to identify novel therapeutic targets for metastatic melanoma. A library of 160 well-characterised and potent protein kinase inhibitors was screened in the BRAF mutant cell line Sk-Mel-28, and the NRAS mutant Sk-Mel-2, using proliferation assays. Of the 160 inhibitors tested, 20 achieved >50% growth inhibition in both cell lines. Six of the 20 were cyclin dependent kinase (CDK) inhibitors, including two CDK4 inhibitors. Fascaplysin, a synthetic CDK4 inhibitor, was further tested in 8 melanoma cell lines. The concentration of fascaplysin required to inhibit growth by 50% (IC50 value) ranged from 0.03 to 0.22 µM. Fascaplysin also inhibited clonogenic growth and induced apoptosis. Sensitivity to PD0332991, a therapeutic CDK4/6 inhibitor was also evaluated in the melanoma cell lines. PD0332991 IC50 values ranged from 0.13 to 2.29 µM. Similar to fascaplysin, PD0332991 inhibited clonogenic growth of melanoma cells and induced apoptosis. Higher levels of CDK4 protein correlated with lower sensitivity to PD0332991 in the cell lines. Combined treatment with PD0332991 and the BRAF inhibitor PLX4032, showed additive anti-proliferative effects in the BRAF mutant cell line Malme-3M. In summary, targeting CDK4 inhibits growth and induces apoptosis in melanoma cells in vitro, suggesting that CDK4 may be a rational therapeutic target for metastatic melanoma.
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