Targeting the IL-6/JAK/STAT3 signalling axis in cancer
By Daniel E. Johnson, Rachel A. O’Keefe, J. Grandis. Nature Reviews Clinical Oncology, 2018
2,754 citations recorded by the source corpus.
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.
Subfields: Epidemiology, Oncology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/4a046dc25bdba84fdfc9d9eb0a896da28753669d
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Citations in the corpus
- Evolving cognition of the JAK-STAT signaling pathway: autoimmune disorders and cancer (2023, background): “Several studies have shown that STAT3 plays a central role in the proliferation, invasion, metastasis, and immune escape of breast cancer cells.(321,322) Moreover, STAT3 helps maintain the phenotype and function of breast cancer stem cells (BCSCs), which display pluripotent properties, resistance to”
- IL-6 in inflammation, autoimmunity and cancer (2020, background): “These multiple signal transduction pathways intimately regulate cell survival, proliferation, inflammation, immunity, angiogenesis, and tumor development and progression through the expression of several genes (1, 19, 21, 26, 31).”
- Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? (2020, neutral): “IL-6 activates its downstream Janus kinase (JAK) signal by binding the transmembrane (cis-signaling) or soluble form (trans-signaling) of the IL-6 receptor (IL-6R) and interacting with membranebound gp130 [29].”