ArticleClinical cancer research : an official journal of the American Association for Cancer Research2010
Inhibition of p-STAT3 enhances IFN-alpha efficacy against metastatic melanoma in a murine model.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The trial behind it
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
29 citing papers in PubMed, 51 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
- Mutual regulations betweenFrontiers in immunology · 2024Review
- Metastatic Melanoma: A Preclinical Model Standardization and Development of a Chitosan-Coated Nanoemulsion Containing Temozolomide to Treat Brain Metastasis.Cellular and molecular neurobiology · 2023Article
- The complementary roles of STAT3 and STAT1 in cancer biology: insights into tumor pathogenesis and therapeutic strategies.Frontiers in immunology · 2023Review
- The Network of Cytokines in Brain Metastases.Cancers · 2021Review
- Intestinal epithelial HMGB1 inhibits bacterial infection via STAT3 regulation of autophagy.Autophagy · 2019Article
- The role of STAT3 in leading the crosstalk between human cancers and the immune system.Cancer letters · 2018Review
- The role of STAT3 in tumor-mediated immune suppression.Journal of neuro-oncology · 2015Review
- Article
- STAT3 Single Nucleotide Polymorphism rs4796793 SNP Does Not Correlate with Response to Adjuvant IFNα Therapy in Stage III Melanoma Patients.Frontiers in medicine · 2014Article
- Drug delivery nanoparticles in skin cancers.BioMed research international · 2014Review
- Therapeutic modulators of STAT signalling for human diseases.Nature reviews. Drug discovery · 2013Review
- The potential for targeting the STAT3 pathway as a novel therapy for melanoma.Future oncology (London, England) · 2013Article
- YB-1 suppression induces STAT3 proteolysis and sensitizes renal cancer to interferon-α.Cancer immunology, immunotherapy : CII · 2013Article
- Variation in susceptibility of human malignant melanomas to oncolytic vesicular stomatitis virus.Surgery · 2013Article
- Regulation of HGF expression by ΔEGFR-mediated c-Met activation in glioblastoma cells.Neoplasia (New York, N.Y.) · 2013Article
- Applications of nanotechnology for melanoma treatment, diagnosis, and theranostics.International journal of nanomedicine · 2013Review
- Article
- Delivery of interferons and siRNA targeting STAT3 using lentiviral vectors suppresses the growth of murine melanoma.Cancer gene therapy · 2012Article
- The tumor microenvironment expression of p-STAT3 influences the efficacy of cyclophosphamide with WP1066 in murine melanoma models.International journal of cancer · 2012Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
purposeMelanoma is a common and deadly tumor that upon metastasis to the central nervous system has a median survival duration of <6 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 malignancy, including immune suppression in melanoma patients. We hypothesized that WP1193, a novel inhibitor of STAT3 signaling, would enhance the antitumor activity of IFN-alpha against metastatic melanoma. EXPERIMENTAL
designCombinational therapy of STAT3 blockade agents with IFN-alpha was investigated in a metastatic and an established syngeneic intracerebral murine tumor model of melanoma. The immunologic in vivo mechanisms of efficacy were investigated by T-cell and natural killer (NK) cell cytotoxic assays.
resultsIFN-alpha immunotherapy was synergistic with WP1193 showing marked in vivo efficacy against metastatic and established intracerebral melanoma. At autopsy, it was noted that there was a decreased trend in mice with melanoma developing leptomeningeal disease treated with combinational therapy. The combinational approach enhanced both NK-mediated and T-cell-mediated antitumor cytotoxicity.
conclusionsThe immune modulatory effects of STAT3 blockade can enhance the therapeutic efficacy of IFN-alpha immunotherapy by enhancing both innate and adaptive cytotoxic T-cell activities. This combination therapy has the potential in the treatment of metastatic melanoma that is typically refractory to this type of immune therapeutic approach.
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Registered trials
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.