ArticleInternational journal of cancer2012
The tumor microenvironment expression of p-STAT3 influences the efficacy of cyclophosphamide with WP1066 in murine melanoma models.
Article in International journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 37 citations in OpenAlex.
- A first-in-human Phase I trial of the oral p-STAT3 inhibitor WP1066 in patients with recurrent malignant glioma.CNS oncology · 2022Trial
- STAT3 silencing by an aptamer-based strategy hampers the crosstalk between NSCLC cells and cancer-associated fibroblasts.Molecular therapy. Nucleic acids · 2023Article
- A Novel Ageladine A Derivative Acts as a STAT3 Inhibitor and Exhibits Potential Antitumor Effects.International journal of molecular sciences · 2023Article
- Overcoming Acquired Drug Resistance to Cancer Therapies through Targeted STAT3 Inhibition.International journal of molecular sciences · 2023Review
- Therapeutic targeting of anoikis resistance in cutaneous melanoma metastasis.Frontiers in cell and developmental biology · 2023Review
- Structure-Activity Study of Nitazoxanide Derivatives as Novel STAT3 Pathway Inhibitors.ACS medicinal chemistry letters · 2021Article
- FOXM1 activates JAK1/STAT3 pathway in human osteoarthritis cartilage cell inflammatory reaction.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Radiation with STAT3 Blockade Triggers Dendritic Cell-T cell Interactions in the Glioma Microenvironment and Therapeutic Efficacy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- STAT3-mediated Apoptotic-enhancing Function of Sclareol Against Breast Cancer Cells and Cell Sensitization to Cyclophosphamide.Iranian journal of pharmaceutical research : IJPR · 2020Article
- STAT3 labels a subpopulation of reactive astrocytes required for brain metastasis.Nature medicine · 2018Article
- Adipose-derived mesenchymal stem cells promote osteosarcoma proliferation and metastasis by activating the STAT3 pathway.Oncotarget · 2017Article
- CXCL12 suppresses cisplatin-induced apoptosis through activation of JAK2/STAT3 signaling in human non-small-cell lung cancer cells.OncoTargets and therapy · 2017Article
- The role of STAT3 in tumor-mediated immune suppression.Journal of neuro-oncology · 2015Review
- MYC Drives Pten/Trp53-Deficient Proliferation and Metastasis due to IL6 Secretion and AKT Suppression via PHLPP2.Cancer discovery · 2015Article
- Preclinical characterization of signal transducer and activator of transcription 3 small molecule inhibitors for primary and metastatic brain cancer therapy.The Journal of pharmacology and experimental therapeutics · 2014Article
- Inhibition of the JAK2/STAT3 pathway reduces gastric cancer growth in vitro and in vivo.PloS one · 2014Article
- Functional involvement of β3-adrenergic receptors in melanoma growth and vascularization.Journal of molecular medicine (Berlin, Germany) · 2013Article
- Stat3-targeted therapies overcome the acquired resistance to vemurafenib in melanomas.The Journal of investigative dermatology · 2013Article
- Variant G6PD levels promote tumor cell proliferation or apoptosis via the STAT3/5 pathway in the human melanoma xenograft mouse model.BMC cancer · 2013Article
- Targeting Tregs in Malignant Brain Cancer: Overcoming IDO.Frontiers in immunology · 2013Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Melanoma is a common and deadly tumor that upon metastasis to the central nervous system (CNS) has median survival duration of less than 5 months. Activation of the signal transducer and activator of transcription 3 (STAT3) has been identified as a key mediator that drives the fundamental components of melanoma. We hypothesized that WP1066, a novel inhibitor of STAT3 signaling, would enhance the antitumor activity of cyclophosphamide (CTX) against melanoma, including disease within the CNS. The mechanisms of efficacy were investigated by tumor- and immune-mediated cytotoxic assays, in vivo evaluation of the reduction of regulatory T cells (Tregs) and by determining intratumoral p-STAT3 expression by immunohistochemistry. Combinational therapy of WP1066, with both metronomic and cytotoxic dosing of CTX, was investigated in a model system of systemic and intracerebral melanoma in syngeneic mice. Inhibition of p-STAT3 by WP1066 was enhanced with CTX in a dose-dependent manner. However, in mice with intracerebral melanoma, the greatest therapeutic benefit was seen in animals treated with cytotoxic CTX dosing and WP1066, whose median survival time was 120 days, an increase of 375%, with 57% long-term survivors. This treatment efficacy correlated with p-STAT3 expression levels within the tumor microenvironment. The efficacy of the combination of cytotoxic dosing of CTX with WP1066 is attributed to the direct tumor cytotoxic effects of the agents and has the greatest therapeutic potential for the treatment of CNS melanoma.
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