Targeting the IL-6/JAK/STAT3 signalling axis in cancer.
Targeting the IL-6/JAK/STAT3 signalling axis in cancer.
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DOI：
10.1038/nrclinonc.2018.8
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发表时间：
2018-04
期刊：
影响因子：
--
通讯作者：
Grandis JR
中科院分区：
文献类型：
--
作者：
Johnson DE;O'Keefe RA;Grandis JR
IL-6/JAK/STAT 3通路在许多类型的癌症中异常地过度活化，并且这种过度活化通常与不良的临床预后相关。在肿瘤微环境中，IL-6/JAK/STAT 3信号传导作用于驱动肿瘤细胞的增殖、存活、侵袭和转移，同时强烈抑制抗肿瘤免疫应答。因此，靶向癌症患者的IL-6/JAK/STAT 3通路的治疗有望通过直接抑制肿瘤细胞生长和刺激抗肿瘤免疫来提供治疗益处。靶向IL-6、IL-6受体或JAK的药物已经获得FDA批准用于治疗炎性疾病或骨髓增生性肿瘤以及管理嵌合抗原受体T细胞的某些不良反应，并且正在造血系统恶性肿瘤患者和实体瘤患者中进行进一步评估。目前正在开发IL-6/JAK/STAT 3途径的新型抑制剂，包括STAT 3选择性抑制剂。在此，我们回顾了IL-6/JAK/STAT 3信号在肿瘤微环境中的作用，以及针对该途径的药物的临床前和临床研究现状。我们还讨论了IL-6/JAK/STAT 3抑制剂与目前批准的针对免疫检查点抑制剂的治疗药物相结合的潜力。
The IL-6/JAK/STAT3 pathway is aberrantly hyperactivated in many types of cancer, and such hyperactivation is generally associated with a poor clinical prognosis. In the tumour microenvironment, IL-6/JAK/STAT3 signalling acts to drive the proliferation, survival, invasiveness, and metastasis of tumour cells, while strongly suppressing the antitumour immune response. Thus, treatments that target the IL-6/JAK/STAT3 pathway in patients with cancer are poised to provide therapeutic benefit by directly inhibiting tumour cell growth and by stimulating antitumour immunity. Agents targeting IL-6, the IL-6 receptor, or JAKs have already received FDA approval for the treatment of inflammatory conditions or myeloproliferative neoplasms and for the management of certain adverse effects of chimeric antigen receptor T cells, and are being further evaluated in patients with haematopoietic malignancies and in those with solid tumours. Novel inhibitors of the IL-6/JAK/STAT3 pathway, including STAT3-selective inhibitors, are currently in development. Herein, we review the role of IL-6/JAK/STAT3 signalling in the tumour microenvironment and the status of preclinical and clinical investigations of agents targeting this pathway. We also discuss the potential of combining IL-6/JAK/STAT3 inhibitors with currently approved therapeutic agents directed against immune-checkpoint inhibitors.
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影响因子：
11.5
作者：
Angevin, Eric;Tabernero, Josep;Kurzrock, Razelle
通讯作者：
Kurzrock, Razelle
影响因子：
15.9
作者：
Bromberg, J
通讯作者：
Bromberg, J
影响因子：
4
作者：
Burel, Sebastien A.;Han, So-Ri;Henry, Scott P.
通讯作者：
Henry, Scott P.
DOI：
10.4161/jkst.20006
发表时间：
2012-04-01
期刊：
JAK-STAT
影响因子：
--
作者：
Bar-Natan M;Nelson EA;Xiang M;Frank DA
通讯作者：
Frank DA
DOI：
10.4161/jkst.23828
发表时间：
2013-04-01
期刊：
JAK-STAT
影响因子：
--
作者：
Bournazou E;Bromberg J
通讯作者：
Bromberg J