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Trends Pharmacol Sci. 2016 Jan;37(1):47-61. doi: 10.1016/j.tips.2015.10.001. Epub 2015 Nov 12.

Feedback Activation of STAT3 as a Cancer Drug-Resistance Mechanism.

Author information

1
School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, People's Republic of China; Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43205, USA; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang 325035, People's Republic of China.
2
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang 325035, People's Republic of China.
3
Department of Medical Laboratory Sciences, University of Delaware, Newark, DE 19716, USA.
4
School of Environmental and Biological Engineering, Nanjing University of Science and Technology, Nanjing, Jiangsu 210094, People's Republic of China. Electronic address: bioshuliny@yahoo.com.cn.
5
Center for Childhood Cancer and Blood Diseases, The Research Institute at Nationwide Children's Hospital, Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43205, USA. Electronic address: lin.674@osu.edu.

Abstract

Signal transducer and activator of transcription 3 (STAT3) plays crucial roles in several cellular processes such as cell proliferation and survival, and has been found to be aberrantly activated in many cancers. Much research has explored the leading mechanisms for regulating the STAT3 pathway and its role in promoting tumorigenesis. We focus here on recent evidence suggesting that feedback activation of STAT3 plays a prominent role in mediating drug resistance to a broad spectrum of targeted cancer therapies and chemotherapies. We highlight the potential of co-targeting STAT3 and its primary target to overcome drug resistance, and provide perspective on repurposing clinically approved drugs as STAT3 pathway inhibitors, in combination with the FDA-approved receptor tyrosine kinase (RTK) inhibitors, to improve clinical outcome of cancer treatment.

KEYWORDS:

STAT3; activation; cancer; drug-resistance; inhibitor

PMID:
26576830
DOI:
10.1016/j.tips.2015.10.001
[Indexed for MEDLINE]

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