Novel inhibitors of the STAT3 signaling pathway: an updated patent review (2014-present)

Wang, Rui; Cao, Xinyu; Lin, Guo‐Qiang; Tian, Ping; Gao, Dingding

doi:10.1080/13543776.2022.2056013

Cited by 3 publications

(1 citation statement)

References 87 publications

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“… 21 Notably, APOJ is recently recognized as one prominent extracellular chaperone in modulating inflammation, extracellular matrix remodeling, proteostasis and signaling transduction in the tumor microenvironment. 22 As a critical signaling transductor, STAT3 functions also as an important transcription factor and participates in the regulation of various immune cells and their crosstalk with TME, 23 suggesting to targeting STAT3 signaling may be a promising option in the tumor immunological treatment field, along with the emergence of new STAT3 inhibitors: 24 in practical, the targeting blockage of STAT3 signaling has shown an exciting efficacy in HBV-related HCC. 25 …”

Section: Introductionmentioning

confidence: 99%

HSF1 is involved in immunotherapeutic response through regulating APOJ/STAT3-mediated PD-L1 expression in hepatocellular carcinoma

Cheng

Wang

Huang

et al. 2022

Cancer Biology & Therapy

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Hepatocellular cancer (HCC) is a serious illness with high prevalence and mortality throughout the whole world. For advanced HCC, immunotherapy is somewhat impactful and encouraging. Nevertheless, a substantial proportion of patients with advanced HCC are still unable to achieve a durable response, owing to heterogeneity from clonal variability and differential expression of the PD-1/PD-L1 axis. Recently, heat shock factor 1 (HSF1) is recognized as an important component of tumor immunotherapeutic response as well as related to PD-L1 expression in cancer. However, the mechanism of HSF1 regulating PD-L1 in cancer, especially in HCC, is still not fully clear. In this study, we observed the significantly positive correlation between HSF1 expression and PD-L1 expression in HCC samples; meanwhile combination expressions of HSF1 and PD-L1 served as the signature for predicting prognosis of patients with HCC. Mechanistically, HSF1 upregulated PD-L1 expression by inducing APOJ expression and activating STAT3 signaling pathway in HCC. In addition, we explored further the potential values of targeting the HSF1-APOJ-STAT3 axis against CD8 + T cells-mediated cancer cells cytotoxicity. These findings unveiled the important involvement of HSF1 in regulating PD-L1 expression in HCC as well as provided a novel invention component for improving the clinical response rate and efficacy of PD-1/PD-L1 blockade.

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Section: Introductionmentioning

confidence: 99%

HSF1 is involved in immunotherapeutic response through regulating APOJ/STAT3-mediated PD-L1 expression in hepatocellular carcinoma

Cheng

Wang

Huang

et al. 2022

Cancer Biology & Therapy

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Azetidine ring, salicylic acid, and salicylic acid bioisosteres as determinants of the binding characteristics of novel potent compounds to Stat3

Chen,

Zhai,

Zhu

et al. 2024

Bioorganic & Medicinal Chemistry Letters

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DNA methylation-mediated repression of microRNA-410 promotes the growth of human glioma cells and triggers cell apoptosis through its interaction with STAT3

Wenfu,

Bin,

Binchan

et al. 2024

Sci Rep

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This study's purpose was to confirm the observed underexpression of miRNA-410 in glioma tissues and several glioma cells by Quantitative RT-PCR. Our findings suggest that epigenetic alterations occurring at the promoter region of miR-410 may be responsible for the reduced expression of miR-410 in glioma. The occurrence of DNA methylation in the miR-410 promoter was verified to be more prevalent through glioma tissues contrasted to adjacent non-tumor brain tissues through the utilization of methylation-specific PCR and CpG bisulfite sequencing sites in the miR-410 promoter region. Accordantly, miR-410 expression in glioma cell lines was observed to be significantly lesser in comparison to that of the human fetal glial cell line. In addition, it was demonstrated through gain- and loss-of-function investigations that miR-410 exerts significant regulation over cell growth, cell cycle development, and glioma cell apoptosis. The findings of the Luciferase reporter assay and western blot analysis indicate that miR-410 has a direct effect on the 3’-UTR of signal transducer and activator of transcription 3 (STAT3), thereby inhibiting its expression within glioma cells. Besides, our clinical investigation indicates a negative association between miR-410 expression and STAT3 within the glioma tissues of humans. In aggregate, the data provided in this investigation indicates that miR-410 is subjected to underexpression via DNA methylation. Furthermore, it has been observed to perform its function as a tumor suppressor in glioma cells through direct targeting of STAT3. The previously mentioned results could potentially have significant implications for the advancement of a new therapeutic approach for treating glioma.

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Novel inhibitors of the STAT3 signaling pathway: an updated patent review (2014-present)

Cited by 3 publications

References 87 publications

HSF1 is involved in immunotherapeutic response through regulating APOJ/STAT3-mediated PD-L1 expression in hepatocellular carcinoma

HSF1 is involved in immunotherapeutic response through regulating APOJ/STAT3-mediated PD-L1 expression in hepatocellular carcinoma

Azetidine ring, salicylic acid, and salicylic acid bioisosteres as determinants of the binding characteristics of novel potent compounds to Stat3

DNA methylation-mediated repression of microRNA-410 promotes the growth of human glioma cells and triggers cell apoptosis through its interaction with STAT3

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