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Arch Pharm Res. 2016 Aug;39(8):1085-99. doi: 10.1007/s12272-016-0795-8. Epub 2016 Aug 11.

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

Kim BH1,2, Yi EH1,3, Ye SK4,5,6,7.

Author information

1
Department of Pharmacology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
2
Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
3
Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
4
Department of Pharmacology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. sangkyu@snu.ac.kr.
5
Biomedical Science Project (BK21PLUS), Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. sangkyu@snu.ac.kr.
6
Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. sangkyu@snu.ac.kr.
7
Neuro-Immune Information Storage Network Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea. sangkyu@snu.ac.kr.

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.

KEYWORDS:

Cancer; Inflammation; Signal transducer and activator of transcription 3 (STAT3); Tumor microenvironment

PMID:
27515050
DOI:
10.1007/s12272-016-0795-8
[Indexed for MEDLINE]

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