Novel activators and small-molecule inhibitors of STAT3 in cancer. (October 2019)

• Record Type: Journal Article
• Authors: Yang, Lehe; Lin, Shichong; Xu, Lingyuan; Lin, Jiayuh; Zhao, Chengguang; Huang, Xiaoying
• Is Part Of: Cytokine & growth factor reviews. Volume 49(2019)
• Page Start: 10
• Page End: 22
• Publication Date: 2019-10
• Subjects: ADAM12 ADAM metallopeptidase domain 12 -- ADME absorption distribution, metabolism and elimination -- AKR1C1 aldo-keto reductase family 1 member C1 -- AKT protein kinase B -- BMX bone marrow and X-linked -- BRAF V-raf murine sarcoma viral oncogene homolog B1 -- CCL2 C-C motif chemokine ligand 2 -- CDK7 cyclin dependent kinase 7 -- ceRNA competing endogenous lncRNA -- EGFR epidermal growth factor receptor -- EMT epithelial-mesenchymal transition -- ERK extracellular regulated protein kinases -- FABP5 fatty acid binding protein 5 -- FEZF1 fasciculation and elongation protein zeta family zinc finger 1 -- FEZF1-AS1 FEZF1 antisense RNA 1 -- FGFR1 fibroblast growth factor receptor 1 -- GSC glioma stem cell -- HCC hepatocellular carcinoma -- HPV18 human papilloma virus 18 -- HSP110 heat shock protein 110 -- HUVECs human umbilical vein endothelial cells -- IL6 interleukin 6 -- JAK2 Janus kinase 2 -- KLF-11 Krüppel-like factor 11 -- lncRNA long noncoding RNA -- MALAT1 metastasis associated lung adenocarcinoma transcript 1 -- MEK MAPK/Erk kinase -- MET mesenchymal to epithelial transition factor -- miRNA MicroRNA -- MKK MAPK kinase -- MTD maximum tolerated dose -- MUC1 Mucin 1 -- NEAT1 nuclear enriched abundant transcript 1 -- NPCs neural progenitor cells -- NSCLC non-small cell lung cancer -- p38 MAPK p38 mitogen activated protein kinases -- PA28γ proteasome activator 28 gamma -- PBX1 PBX homeobox 1 -- PIAS3 rotein inhibitor of activated STAT 3 -- PVT1 plasmacytoma variant translocation 1 -- Rac1 ras-related C3 botulinum toxin substrate 1 -- RanBP6 RAN binding protein 6 -- Ras rat sarcoma -- RTKs receptor tyrosine kinases -- Smads drosophila mothers against decapentaplegic proteins -- SOCS3 suppressor of cytokine signaling 3 -- SOX2 SRY-box 2 -- Src sarcoma gene proto-oncogene, non-receptor tyrosine kinase -- STAT3 signal transducer and activator of transcription 3 -- TALE three amino acid loop extension -- TC45 T-cell protein-tyrosine phosphatase(45kd) -- TGF-β transforming growth factor beta -- TKI tyrosine kinase inhibitor -- TRIM tripartite motif containing -- USP22 ubiquitin specific peptidase 22 -- VEGFA vascular endothelial growth factor A -- XIST X inactive specific transcript -- YAP yes associated protein; STAT3 -- Activator -- Cancer -- Signal pathway -- Inhibitor; Cytokines -- Periodicals; 571.84
• DOI: 10.1016/j.cytogfr.2019.10.005
• Languages: English
• ISSNs: 1359-6101

Abstract

Graphical abstract: Highlights: Novel activators of STAT3 have diverse functions in regulating cancer cellular processes and have been validated as potential drug targets. STAT3 activation is a resistance mechanism. STAT3 inhibitors that show promise as new therapeutic leads can combined with chemotherapies to improve patient outcomes. Abstract: Excessive activation of signal transducer and activator of transcription 3 (STAT3) signaling is observed in a subset of many cancers, making activated STAT3 a highly promising potential therapeutic target supported by multiple preclinical and clinical studies. However, early-phase clinical trials have produced mixed results with STAT3-targeted cancer therapies, revealing substantial complexity to targeting aberrant STAT3 signaling. This review discusses the diverse mechanisms of oncogenic activation of STAT3, and the small molecule inhibitors of STAT3 in cancer treatment.