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

被引：122

作者：

Beebe, Jenny D. ^{[1
]}

Liu, Jing-Yuan ^{[1
,2
]}

Zhang, Jian-Ting ^{[1
,3
]}

机构：

[1] Indiana Univ Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA

[2] Indiana Univ Purdue Univ, Dept Comp & Informat Sci, Indianapolis, IN 46202 USA

[3] Indiana Univ Sch Med, IU Simon Canc Ctr, 980 W Walnut St,R3-0510, Indianapolis, IN 46202 USA

来源：

PHARMACOLOGY & THERAPEUTICS | 2018年 / 191卷

关键词：

STAT3; inhibitor; cancer therapeutics; drug discovery; small molecule compounds; molecular probes; clinical trials; DNA-BINDING DOMAIN; GROWTH-SUPPRESSIVE ACTIVITY; TRANSCRIPTION FACTOR STAT3; SMALL-MOLECULE INHIBITORS; COILED-COIL DOMAIN; CELL-CYCLE ARREST; SIGNAL TRANSDUCER; COLON-CANCER; CONSTITUTIVE STAT3; ANTITUMOR-ACTIVITY;

D O I：

10.1016/j.pharmthera.2018.06.006

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

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. (C) 2018 Elsevier Inc. All rights reserved.

引用

页码：74 / 91

页数：18

共 190 条

[1]

Targeting STAT3 inhibits growth and enhances radiosensitivity in head and neck squamous cell carcinoma [J].

Adachi, Makoto ;

Cui, Caixia ;

Dodge, Cristina T. ;

Bhayani, Mihir K. ;

Lai, Stephen Y. .

ORAL ONCOLOGY, 2012, 48 (12) :1220-1226

[2]

Glioma Cell Migration on Three-dimensional Nanofiber Scaffolds Is Regulated by Substrate Topography and Abolished by Inhibition of STAT3 Signaling [J].

Agudelo-Garcia, Paula A. ;

De Jesus, Jessica K. ;

Williams, Shante P. ;

Nowicki, Michal O. ;

Chiocca, Ennio Antonio ;

Liyanarachchi, Sandya ;

Li, Pui-Kai ;

Lannutti, John J. ;

Johnson, Jed K. ;

Lawler, Sean E. ;

Viapiano, Mariano S. .

NEOPLASIA, 2011, 13 (09) :831-U96

[3]

STA-21, a STAT-3 inhibitor, attenuates the development and progression of inflammation in collagen antibody-induced arthritis [J].

Ahmad, Sheikh Fayaz ;

Ansari, Mushtaq Ahmad ;

Nadeem, Ahmed ;

Zoheir, Khairy M. A. ;

Bakheet, Saleh A. ;

Alsaad, Abdulaziz M. S. ;

Al-Shabanah, Othman A. ;

Attia, Sabry M. .

IMMUNOBIOLOGY, 2017, 222 (02) :206-217

[4]

The anti-tumor activity of the STAT3 inhibitor STX-0119 occurs via promotion of tumor-infiltrating lymphocyte accumulation in temozolomide-resistant glioblastoma cell line [J].

Akiyama, Yasuto ;

Nonomura, Chizu ;

Ashizawa, Tadashi ;

Iizuka, Akira ;

Kondou, Ryota ;

Miyata, Haruo ;

Sugino, Takashi ;

Mitsuya, Koichi ;

Hayashi, Nakamasa ;

Nakasu, Yoko ;

Asai, Akira ;

Ito, Mamoru ;

Kiyohara, Yoshio ;

Yamaguchi, Ken .

IMMUNOLOGY LETTERS, 2017, 190 :20-25

[5]

Rheumatoid arthritis: Recent advances on its etiology, role of cytokines and pharmacotherapy [J].

Alam, Javaid ;

Jantan, Ibrahim ;

Bukhari, Syed Nasir Abbas .

BIOMEDICINE & PHARMACOTHERAPY, 2017, 92 :615-633

[6]

Induced somatic inactivation of STAT3 in mice triggers the development of a fulminant form of enterocolitis [J].

Alonzi, T ;

Newton, IP ;

Bryce, PJ ;

Di Carlo, E ;

Lattanzio, G ;

Tripodi, M ;

Musiani, P ;

Poli, V .

CYTOKINE, 2004, 26 (02) :45-56

[7]

Signal transducer and activator of transcription 3 is required for the oncogenic effects of non-small-cell lung cancer-associated mutations of the epidermal growth factor receptor [J].

Alvarez, JV ;

Greulich, H ;

Sellers, WR ;

Meyerson, M ;

Frank, DA .

CANCER RESEARCH, 2006, 66 (06) :3162-3168

[8]

Activating somatic mutations outside the SH2-domain of STAT3 in LGL leukemia [J].

Andersson, E. ;

Kuusanmaki, H. ;

Bortoluzzi, S. ;

Lagstrom, S. ;

Parsons, A. ;

Rajala, H. ;

van Adrichem, A. ;

Eldfors, S. ;

Olson, T. ;

Clemente, M. J. ;

Laasonen, A. ;

Ellonen, P. ;

Heckman, C. ;

Loughran, T. P. ;

Maciejewski, J. P. ;

Mustjoki, S. .

LEUKEMIA, 2016, 30 (05) :1204-1208

[9]

Applying Small Molecule Signal Transducer and Activator of Transcription-3 (STAT3) Protein Inhibitors as Pancreatic Cancer Therapeutics [J].

Arpin, Carolyn C. ;

Mac, Stephen ;

Jiang, Yanlin ;

Cheng, Huiwen ;

Grimard, Michelle ;

Page, Brent D. G. ;

Kamocka, Malgorzata M. ;

Haftchenary, Sina ;

Su, Han ;

Ball, Daniel P. ;

Rosa, David A. ;

Lai, Ping-Shan ;

Gomez-Biagi, Rodolfo F. ;

Ali, Ahmed M. ;

Rana, Rahul ;

Hanenberg, Helmut ;

Kerman, Kagan ;

McElyea, Kyle C. ;

Sandusky, George E. ;

Gunning, Patrick T. ;

Fishel, Melissa L. .

MOLECULAR CANCER THERAPEUTICS, 2016, 15 (05) :794-805

[10]

Effect of the STAT3 inhibitor STX-0119 on the proliferation of a temozolomide-resistant glioblastoma cell line [J].

Ashizawa, Tadashi ;

Akiyama, Yasuto ;

Miyata, Haruo ;

Iizuka, Akira ;

Komiyama, Masaru ;

Kume, Akiko ;

Omiya, Maho ;

Sugino, Takashi ;

Asai, Akira ;

Hayashi, Nakamasa ;

Mitsuya, Koichi ;

Nakasu, Yoko ;

Yamaguchi, Ken .

INTERNATIONAL JOURNAL OF ONCOLOGY, 2014, 45 (01) :411-418

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