title: Feedback Activation of STAT3 as a Cancer Drug-Resistance Mechanism.
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.
authors.affiliation: 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.
authors.forename: Chengguang
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang 325035, People's Republic of China.
authors.forename: Huameng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Medical Laboratory Sciences, University of Delaware, Newark, DE 19716, USA.
authors.forename: Huey-Jen
authors.initials: HJ
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Shulin
authors.initials: S
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Jiayuh
authors.initials: J
authors.lastname: Lin
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang 325035, People's Republic of China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
mesh_terms: D000818:Animals; D019008:Drug Resistance, Neoplasm; D025461:Feedback, Physiological; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*
chemical_list: D050796:STAT3 Transcription Factor
keywords: STAT3; activation; cancer; drug-resistance; inhibitor