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Signal transducer and activator of transcription 3 as a therapeutic target for cancer and the tumor microenvironment

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Abstract

Signal transducer and activator of transcription 3 (STAT3) is a cytoplasmic transcription factor that modulates the transcription of a variety of genes to regulate important biological functions, including cell proliferation, differentiation, survival, angiogenesis, and immune response. Constitutive activation of STAT3 is important in oncogenic signaling and occurs at high frequency in human cancers, including diverse solid tumors and hematologic malignancies. Moreover, it is associated with a poor prognosis. The tumor microenvironment has recently been recognized as a key condition for cancer progression, invasion, angiogenesis, metastasis, and drug resistance by activation of STAT3 signaling. Therefore, understanding the biology associated with STAT3-mediated signaling cascades in the tumor microenvironment may offer the therapeutic potential to treat human cancers. This review presents an overview of the critical roles of STAT3 in the tumor microenvironment related to cancer biology and discusses recent advancements in the development of anticancer drugs that therapeutically inhibit STAT3 signaling cascades.

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Acknowledgments

This study was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korea government (MESF; 2012R1A2A2A01012897 and 2014R1A2A1A11053203, and MISP; 2012R1A5A2A44671346), the National R&D program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (0720540), the Seoul National University Hospital (SNUH) Research Fund (3420130270 and 0320140100), and the Cooperative Research Program of Basic Medical Science and Clinical Science from Seoul National University College of Medicine (800-20160092).

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  1. Department of Pharmacology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea

    Byung-Hak Kim, Eun Hee Yi & Sang-Kyu Ye

  2. Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea

    Byung-Hak Kim & Sang-Kyu Ye

  3. Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea

    Eun Hee Yi & Sang-Kyu Ye

  4. Neuro-Immune Information Storage Network Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea

    Sang-Kyu Ye

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Kim, BH., Yi, E.H. & Ye, SK. Signal transducer and activator of transcription 3 as a therapeutic target for cancer and the tumor microenvironment. Arch. Pharm. Res. 39, 1085–1099 (2016). https://doi.org/10.1007/s12272-016-0795-8

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