ArticlePloS one2014
Targeting Bcl-2/Bcl-XL induces antitumor activity in uveal melanoma patient-derived xenografts.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 49 citations in OpenAlex.
- Novel CRISPR-Cas9 BAP1 knockout pre-clinical tumor model recapitulates human melanoma tumorigenesis and immune evolution.Communications biology · 2026Article
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- Current Advances and Future Strategies for BCL-2 Inhibitors: Potent Weapons against Cancers.Cancers · 2023Review
- Cannabidiol regulates apoptosis and autophagy in inflammation and cancer: A review.Frontiers in pharmacology · 2023Review
- Palmitoylation of GNAQ/11 is critical for tumor cell proliferation and survival in GNAQ/11-mutant uveal melanoma.Frontiers of medicine · 2022Article
- Expression Differences in BCL2 Family Members between Uveal and Cutaneous Melanomas Account for Varying Sensitivity to BH3 Mimetics.The Journal of investigative dermatology · 2022Article
- Targeting the BCL-2-regulated apoptotic pathway for the treatment of solid cancers.Biochemical Society transactions · 2021Review
- Hypoxia-dependent drivers of melanoma progression.Journal of experimental & clinical cancer research : CR · 2021Review
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- Targeting apoptosis in cancer therapy.Nature reviews. Clinical oncology · 2020Review
- Inhibition of Anti-Apoptotic Bcl-2 Proteins in Preclinical and Clinical Studies: Current Overview in Cancer.Cells · 2020Review
- Review
- Mouse models of uveal melanoma: Strengths, weaknesses, and future directions.Pigment cell & melanoma research · 2020Review
- Endoplasmic reticulum stress mediates resistance to BCL-2 inhibitor in uveal melanoma cells.Cell death discovery · 2020Article
- Transcriptional inhibition by CDK7/9 inhibitor SNS-032 abrogates oncogene addiction and reduces liver metastasis in uveal melanoma.Molecular cancer · 2019Article
- Emerging Therapeutic Opportunities Based on Current Knowledge of Uveal Melanoma Biology.Cancers · 2019Review
- Article
- Article
- Demethylzeylasteral inhibits cell proliferation and induces apoptosis through suppressing MCL1 in melanoma cells.Cell death & disease · 2017Article
- Progress in targeting the BCL-2 family of proteins.Current opinion in chemical biology · 2017Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeUveal melanoma (UM) is associated with a high risk of metastases and lack of efficient therapies. Reduced capacity for apoptosis induction by chemotherapies is one obstacle to efficient treatments. Human UM is characterized by high expression of the anti-apoptotic protein Bcl-2. Consequently, regulators of apoptosis such as Bcl-2 family inhibitors may constitute an attractive approach to UM therapeutics. In this aim, we have investigated the efficacy of the Bcl-2/Bcl-XL inhibitor S44563 on 4 UM Patient-Derived Xenografts (PDXs) and derived-cell lines. EXPERIMENTAL
designFour well characterized UM PDXs were used for in vivo experiments. S44563 was administered alone or combined with fotemustine either concomitantly or after the alkylating agent. Bcl-2, Bcl-XL, and Mcl-1 expressions after S44563 administration were evaluated by immunohistochemistry (IHC).
resultsS44563 administered alone by at 50 and 100 mg/kg i.p. induced a significant tumour growth inhibition in only one xenograft model with a clear dose effect. However, when S44563 was concomitantly administered with fotemustine, we observed a synergistic activity in 3 out of the 4 tested models. In addition, S44563 administered after fotemustine induced a tumour growth delay in 2 out of 3 tested xenografts. Finally, IHC analyses showed that Bcl-2, Bcl-XL, and Mcl-1 expression were not modified after S44563 administration.
conclusionThe novel anti-apoptotic experimental compound S44563, despite a relative low efficacy when administered alone, increased the efficacy of fotemustine in either concomitant or sequential combinations or indeed subsequent to fotemustine. These data support further exploration of potential therapeutic effect of Bcl-2/Bcl-xl inhibition in human UM.
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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.