gw-3965 and Melanoma

gw-3965 has been researched along with Melanoma* in 2 studies

Other Studies

2 other study(ies) available for gw-3965 and Melanoma

ArticleYear
Activation of LXRβ inhibits tumor respiration and is synthetically lethal with Bcl-xL inhibition.
    EMBO molecular medicine, 2019, Volume: 11, Issue:10

    Liver-X-receptor (LXR) agonists are known to bear anti-tumor activity. However, their efficacy is limited and additional insights regarding the underlying mechanism are necessary. By performing transcriptome analysis coupled with global polar metabolite screening, we show that LXR agonists, LXR623 and GW3965, enhance synergistically the anti-proliferative effect of BH3 mimetics in solid tumor malignancies, which is predominantly mediated by cell death with features of apoptosis and is rescued by exogenous cholesterol. Extracellular flux analysis and carbon tracing experiments (U-

    Topics: Animals; Apoptosis; bcl-X Protein; Benzoates; Benzylamines; Carcinoma; Cell Proliferation; Cell Respiration; Disease Models, Animal; Gene Expression Profiling; Glioblastoma; Humans; Indazoles; Liver X Receptors; Melanoma; Metabolomics; Models, Theoretical; Treatment Outcome

2019
Broad-spectrum therapeutic suppression of metastatic melanoma through nuclear hormone receptor activation.
    Cell, 2014, Feb-27, Volume: 156, Issue:5

    Melanoma metastasis is a devastating outcome lacking an effective preventative therapeutic. We provide pharmacologic, molecular, and genetic evidence establishing the liver-X nuclear hormone receptor (LXR) as a therapeutic target in melanoma. Oral administration of multiple LXR agonists suppressed melanoma invasion, angiogenesis, tumor progression, and metastasis. Molecular and genetic experiments revealed these effects to be mediated by LXRβ, which elicits these outcomes through transcriptional induction of tumoral and stromal apolipoprotein-E (ApoE). LXRβ agonism robustly suppressed tumor growth and metastasis across a diverse mutational spectrum of melanoma lines. LXRβ targeting significantly prolonged animal survival, suppressed the progression of established metastases, and inhibited brain metastatic colonization. Importantly, LXRβ activation displayed melanoma-suppressive cooperativity with the frontline regimens dacarbazine, B-Raf inhibition, and the anti-CTLA-4 antibody and robustly inhibited melanomas that had acquired resistance to B-Raf inhibition or dacarbazine. We present a promising therapeutic approach that uniquely acts by transcriptionally activating a metastasis suppressor gene.

    Topics: Animals; Apolipoproteins E; Benzoates; Benzylamines; Cells, Cultured; Disease Models, Animal; Humans; Hydrocarbons, Fluorinated; Liver X Receptors; Melanoma; Mice; Neoplasm Metastasis; Orphan Nuclear Receptors; Signal Transduction; Skin Neoplasms; Sulfonamides; Transcription, Genetic

2014
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