The JAK/STAT3 axis: A comprehensive drug target for solid malignancies

被引:162
作者
Huynh, Jennifer [1 ,2 ]
Etemadi, Nima [1 ,2 ]
Hollande, Frederic [3 ]
Ernst, Matthias [1 ,2 ]
Buchert, Michael [1 ,2 ]
机构
[1] Olivia Newton John Canc Res Inst, 145 Studely Rd, Heidelberg, Vic 3084, Australia
[2] La Trobe Univ, Sch Canc Med, 145 Studely Rd, Heidelberg, Vic 3084, Australia
[3] Univ Melbourne, Dept Pathol, Victorian Comprehens Canc Ctr, Grattan St, Parkville, Vic 3010, Australia
基金
澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;
关键词
Signal transducer and activator of transcription 3 (STAT3); Janus kinase (JAK); Tumor development; Immunosuppression; Immunotherapy; CANCER-ASSOCIATED FIBROBLASTS; TUMOR-ASSOCIATED MACROPHAGES; REGULATORY T-CELLS; EPIDERMAL-GROWTH-FACTOR; JANUS KINASE INHIBITOR; SUPPRESSOR-CELLS; INFILTRATING MACROPHAGES; PANCREATIC-CANCER; SIGNAL TRANSDUCERS; STAT3; ACTIVATION;
D O I
10.1016/j.semcancer.2017.06.001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Intercellular communication between tumor cells, immune cells and the stroma characterises the tumor microenvironment, which is instrumental for establishing the ecological niche that fosters tumor growth and metastasis. While tumor cell intrinsic STAT3 signaling provides a crucial axis to support cell proliferation and survival, it also regulates many activities of the non-transformed cells that collectively make up the tumor microenvironment. Accordingly, excessive activation of STAT3 is a hallmark of many malignancies, and often occurs in response to cytokines of the IL-6 and IL-10 families. However, tumor extrinsic STAT3 signaling also regulates the effector function of tumor-associated immune and stromal cells, which support the growth of tumors by suppressing the host's anti-tumor immune response. Given that STAT3 mediates tumorigenic effects in many cell types, the molecular players of STAT3 signaling and its upstream JAR kinases provide viable therapeutic targets for the treatment of cancer. Here we provide an update on novel insights into the role of STAT3 in immune suppression and describe current therapeutic strategies that target the JAK/STAT3 signaling axis for the treatment of malignancies.
引用
收藏
页码:13 / 22
页数:10
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