STAT3 inhibitor stattic enhances radiosensitivity in esophageal squamous cell carcinoma

Qu, Zhipeng; Zhang, Chi; He, Jia; Guo, Qing; Hu, Desheng; Yang, Xi; Wang, Jinfeng; Kang, Yahui; She, Ruifang; Wang, Zhongming; Li, Defan; Huang, Guanhong; Ma, Zhaoming; Mao, Weidong; Zhou, Xiaoyi; Xiao, Changhong; Sun, Xinchen; Ma, Jianxin

doi:10.1007/s13277-014-2823-y

Cited by 52 publications

(34 citation statements)

References 24 publications

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“…First, siRNA-mediated IL-6 inhibition in ESCC cell lines resulted in enhanced chemosensitivity and increased cell death, decreased angiogenesis and less epithelial-to-mesenchymal transition (EMT) 59,63 . Furthermore, inhibition of STAT3 signaling by small molecules like stattic radio-sensitized ESCC cells in vivo 64 . Stattic also induced apoptosis in BE and EAC cells and restored chemo- and radio-sensitivity 65,66 .…”

Section: Inflammatory Signaling Pathways Promote Cell Proliferation Amentioning

confidence: 99%

The tumor microenvironment in esophageal cancer

et al. 2016

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Esophageal cancer is a deadly disease, ranking sixth among all cancers in mortality. Despite incremental advances in diagnostics and therapeutics, esophageal cancer still carries a poor prognosis, and thus there remains a need to elucidate the molecular mechanisms underlying this disease. There is accumulating evidence that a comprehensive understanding of the molecular composition of esophageal cancer requires attention to not only tumor cells but also the tumor microenvironment, which contains diverse cell populations, signaling factors, and structural molecules that interact with tumor cells and support all stages of tumorigenesis. In esophageal cancer, environmental exposures can trigger chronic inflammation, which leads to constitutive activation of pro-inflammatory signaling pathways that promote survival and proliferation. Anti-tumor immunity is attenuated by cell populations such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), as well as immune checkpoints like programmed death-1 (PD-1). Other immune cells such as tumor-associated macrophages can have other pro-tumorigenic functions, including the induction of angiogenesis and tumor cell invasion. Cancer-associated fibroblasts secrete growth factors and alter the extracellular matrix (ECM) to create a tumor niche and enhance tumor cell migration and metastasis. Further study of how these TME components relate to the different stages of tumor progression in each esophageal cancer subtype will lead to development of novel and specific TME-targeting therapeutic strategies, which offer considerable potential especially in the setting of combination therapy.

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Section: Inflammatory Signaling Pathways Promote Cell Proliferation Amentioning

confidence: 99%

The tumor microenvironment in esophageal cancer

et al. 2016

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“…Additionally, combination treatments of Stattic with other chemotherapeutics, such as temozolomide, cisplatin, Herceptin, and radiation increased the efficacy of these treatments, leading to increased apoptosis in glioma, head and neck squamous cell carcinoma (HNSCC), and breast cancer cells (Adachi, et al, 2012;Chung, et al, 2014;Pan, Zhou, Zhang, & Claret, 2013;Villalva, et al, 2011). Stattic has also been tested in several animal models such as, HNSCC, esophageal squamous cell carcinoma, colon, prostate and ovarian cancer, which showed that Stattic alone reduced tumor growth and has enhanced effect when given in combination with radiation and chemotherapeutic treatments (Adachi, et al, 2012;Han, et al, 2014;Ji, et al, 2013;Spitzner, et al, 2014;Q. Zhang, et al, 2015).…”

Section: Small Molecule Inhibitors Targeting the Sh2 Domainmentioning

confidence: 99%

Two decades of research in discovery of anticancer drugs targeting STAT3, how close are we?

Beebe

Liu

Zhang

2018

Pharmacology & Therapeutics

118

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Signal transducer and activator of transcription 3 (STAT3) controls many biological processes including differentiation, survival, proliferation, and angiogenesis. In normal healthy cells, STAT3 is tightly regulated to maintain a momentary active state. However, aberrant or constitutively activated STAT3 has been observed in many different cancers and constitutively activated STAT3 has been shown to associate with poor prognosis and tumor progression. For this reason, STAT3 has been studied as a possible target in the treatment of many different types of cancers. However, despite decades of research, a FDA-approved STAT3 inhibitor has yet to emerge. In this review, we will analyze past studies targeting STAT3 for drug discovery, understand possible causes of failure in these studies, and provide potential insights for future efforts to overcome these roadblocks.

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“…Other recently developed inhibitors targeting the SH2 domain of STAT3 include S3I-201 [125], its analog S3I-1757 [126], STA-21, and its derivatives LLL-3 and LLL-12 [127][128][129]. Effectiveness of these inhibitors in STAT3 inhibition has been tested in solid cancers [128,[130][131][132]. The small peptide aptamer DBD-1 is an STAT3 DBD inhibitor, which prevents STAT3 from DNA binding but does not affect STAT3 activation [133].…”

Section: Direct Stat3 Inhibitionmentioning

confidence: 99%

STAT3 Activation and Oncogenesis in Lymphoma

Zhu

Wang²,

2019

Cancers

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Signal transducer and activator of transcription 3 (STAT3) is an important and the most studied transcription factor in the Janus kinase (JAK)/STAT signaling pathway. STAT3 mediates the expression of various genes that play a critical role in many cellular and biological processes, such as cell proliferation, survival, differentiation, migration, angiogenesis, and inflammation. STAT3 and associated JAKs are activated and tightly regulated by a variety of cytokines and growth factors and their receptors in normal immune responses. However, abnormal expression of STAT3 leads to its constitutive activation, which promotes malignant transformation and tumor progression through oncogenic gene expression in numerous human cancers. Human lymphoma is a heterogeneous malignancy of T and B lymphocytes. Constitutive signaling by STAT3 is an oncogenic driver in several types of B-cell lymphoma and most of T-cell lymphomas. Aberrant STAT3 activation can also induce inappropriate expression of genes involved in tumor immune evasion such as PD-L1. In this review, we focus on the oncogenic role of STAT3 in human lymphoma and highlight potential therapeutic intervention by targeting JAK/STAT3 signaling.

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STAT3 inhibitor stattic enhances radiosensitivity in esophageal squamous cell carcinoma

Cited by 52 publications

References 24 publications

The tumor microenvironment in esophageal cancer

The tumor microenvironment in esophageal cancer

Two decades of research in discovery of anticancer drugs targeting STAT3, how close are we?

STAT3 Activation and Oncogenesis in Lymphoma

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