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Nat Rev Cancer. 2019 Feb;19(2):82-96. doi: 10.1038/s41568-018-0090-8.

Therapeutically exploiting STAT3 activity in cancer - using tissue repair as a road map.

Author information

1
Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria, Australia.
2
Centre for Cancer Research, Hudson Institute of Medical Research, Clayton, Victoria, Australia. Daniel.Gough@monash.edu.
3
Department of Molecular and Translational Science, Monash University, Clayton, Victoria, Australia. Daniel.Gough@monash.edu.
4
Olivia Newton-John Cancer Research Institute and La Trobe University School of Cancer Medicine, Heidelberg, Victoria, Australia. Matthias.Ernst@onjcri.org.au.

Abstract

The tightly orchestrated temporal and spatial control of signal transducer and activator of transcription 3 (STAT3) activity in epithelial, immune and stromal cells is critical for wound healing and tissue repair. Excessive STAT3 activation within cancer cells and cells of the tumour microenvironment can be viewed as a neoplastic mimic of an inflammation-driven repair response that collectively promotes tumour progression. In addition to the canonical transcriptional pathways by which STAT3 promotes stem cell-like characteristics, survival, proliferation, metastatic potential and immune evasion, cytoplasmic STAT3 activity fuels tumour growth by metabolic and other non-transcriptional mechanisms. Here, we review the tumour-modulating activities of STAT3 in light of its role as a signalling node integrating inflammatory responses during wound healing. Accordingly, many of the cytokines that contribute to the para-inflammatory state of most solid malignancies converge on and underpin dysregulated STAT3 activity. Targeting of these cytokines, their cognate receptors and associated signalling cascades in clinical trials is beginning to demonstrate therapeutic efficacy, given that interference with STAT3 activity is likely to simultaneously curb the growth of cancer cells and augment antitumour immunity.

PMID:
30578415
DOI:
10.1038/s41568-018-0090-8
[Indexed for MEDLINE]

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