ArticleTherapeutic advances in medical oncology2020
Navitoclax combined with Alpelisib effectively inhibits Merkel cell carcinoma cell growth
Article in Therapeutic advances in medical oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- Navitoclax-encapsulated dual pH-responsive copolymeric nanoparticles improves hepatocellular carcinoma treatment with induction of apoptosis and immune activation.Journal of nanobiotechnology · 2026Article
- Injectable Senolytic Hydrogel Depot for the Clearance of Senescent Cells.Biomacromolecules · 2025Article
- Article
- Therapeutic Approaches for Non-Melanoma Skin Cancer: Standard of Care and Emerging Modalities.International journal of molecular sciences · 2024Review
- Merkel cell carcinoma: updates in tumor biology, emerging therapies, and preclinical models.Frontiers in oncology · 2024Review
- Article
- Co-Targeting MAP Kinase and Pi3K-Akt-mTOR Pathways in Meningioma: Preclinical Study of Alpelisib and Trametinib.Cancers · 2022Article
- Therapeutic Potential of 5'-Methylschweinfurthin G in Merkel Cell Polyomavirus-Positive Merkel Cell Carcinoma.Viruses · 2022Article
- Programmed cell death, redox imbalance, and cancer therapeutics.Apoptosis : an international journal on programmed cell death · 2021Review
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMerkel cell carcinoma (MCC) is a highly malignant skin cancer. Despite major treatment improvements during the last decade, up to 50% of patients do not respond to therapy or develop recurrent disease. For these patients, alternative treatment options are urgently needed. Here, we assessed the efficacy of the combination of the BCL-2 inhibitor Navitoclax and the PI3K p110α inhibitor Alpelisib in MCC cell lines.
methodsThe expression of BCL-2 was assessed by immunohistochemistry in MCC and MCC cell lines. Treatment with Navitoclax and Alpelisib alone and in combination was performed on four MCC cell lines. The decrease of cell viability during treatment was assessed by XTT assay and visualized for the combinations by 3D combinatorial index plotting. The increase of apoptotic cells was determined by cleaved PARP Western blotting and Annexin V staining.
resultsSome 94% of MCCs and all three MCPyV-positive cell lines showed BCL-2 expression. Navitoclax monotreatment was shown to be highly effective when treating BCL-2-positive cell lines (IC DISCUSSION: Our results show that the anti-apoptotic BCL-2 is frequently expressed in MCC and MCC cell lines. Inhibition of BCL-2 by Navitoclax in combination with Alpelisib revealed a strong synergy and prolonged inhibition of MCC cell viability and induction of apoptosis. The combination of Navitoclax and Alpelisib is a novel potential treatment option for MCC patients.
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