Evidence map›Paper›PMID 39893129›Full record

ReviewCytokine & growth factor reviews2025

Insights into IL-6/JAK/STAT3 signaling in the tumor microenvironment: Implications for cancer therapy.

Win Lwin Thuya, Yang Cao, Paul Chi-Lui Ho, Andrea Li-Ann Wong, Lingzhi Wang, Jianbiao Zhou, Christophe Nicot, Boon Cher Goh

Abstract readReview
In one paragraph

Review in Cytokine & growth factor reviews, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
84citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

84 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  16. ANXA2-mediated Phagocytosis Generates ARAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  19. In Vitro Biological Activities of Piper corcovadensis C.DC.: Antioxidant, Antineoplastic-Related and Antibacterial Effects.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  20. Review

24 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Win Lwin ThuyaCancer Science Institute of Singapore, National University of Singapore, 117599, Singapore.
Yang CaoCancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Laboratory Medicine, Lequn Brance, The First Hospital of Jilin University, Changchun, Jilin 130031, China.
Paul Chi-Lui HoSchool of Pharmacy, Monash University Malaysia, Bandar Sunway, Jalan Lagoon, Selangor Darul Ehsan 47500, Malaysia.
Andrea Li-Ann WongCancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, 117599, Singapore; Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, USA.
Lingzhi WangCancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore. Electronic address: csiwl@nus.edu.sg.
Jianbiao ZhouCancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, 117599, Singapore. Electronic address: csizjb@nus.edu.sg.
Christophe NicotDepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, USA.
Boon Cher GohCancer Science Institute of Singapore, National University of Singapore, 117599, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; NUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 117600, Singapore; Department of Haematology-Oncology, National University Cancer Institute, National University Health System, 119074, Singapore.

Funding

Transgenic & Gene-Targeting Shared ResourceP30CA168524 · NCI · UNIVERSITY OF KANSAS MEDICAL CENTER · PI ROY A. JENSEN · 2012 to 2026
$40.1M
NCI NIH HHS P30 CA168524
6 · The paper itself

Abstract

The IL-6/JAK/STAT3 signaling pathway is a key regulator of tumor progression, immune evasion, and therapy resistance in various cancers. Frequently dysregulated in malignancies, this pathway drives cancer cell growth, survival, angiogenesis, and metastasis by altering the tumor microenvironment (TME). IL-6 activates JAK kinases and STAT3 through its receptor complex, leading to the transcription of oncogenic genes and fostering an immunosuppressive TME. This environment recruits tumor-associated macrophages (TAMs), cancer-associated fibroblasts (CAFs), and regulatory T cells (Tregs), collectively supporting immune evasion and tumor growth. IL-6/JAK/STAT3 axis also contributes to metabolic reprogramming, such as enhanced glycolysis and glutathione metabolism, helping cancer cells adapt to environmental stresses. Therapeutic targeting of this pathway has gained significant interest. Strategies include monoclonal antibodies against IL-6 or its receptor (e.g., Tocilizumab, Siltuximab), JAK inhibitors (e.g., Ruxolitinib), and STAT3-specific inhibitors (e.g., Napabucasin), which have exhibited promise in preclinical and initial clinical studies. These inhibitors can suppress tumor growth, reverse immune suppression, and enhance the efficacy of immunotherapies like immune checkpoint inhibitors. Combination therapies that integrate IL-6 pathway inhibitors with conventional treatments are particularly promising, addressing resistance mechanisms and improving patient outcomes. Advances in biomarker-driven patient selection, RNA-based therapies, and isoform-specific inhibitors pave the way for more precise interventions. This review delves into the diverse roles of IL-6/JAK/STAT3 signaling in cancer progression, therapeutic strategies targeting this pathway, and the potential for integrating these approaches into personalized medicine to enhance treatment outcomes.

Indexed as

Interleukin-6Janus KinasesNeoplasmsSignal TransductionSTAT3 Transcription FactorTumor MicroenvironmentAnimalsHumansIL6 protein, humanInterleukin-6Janus KinasesSTAT3 protein, humanSTAT3 Transcription FactorCancer immunotherapyCytokine signalingIL-6 signalingJAK/STAT3 pathwayTumor microenvironment (TME)

Identifiers

PMID39893129
PMCPMC13560456

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.