Unraveling the complexity of STAT3 in cancer: molecular understanding and drug discovery

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional factor involved in almost all cancer hallmark features including tumor proliferation, metastasis, angiogenesis, immunosuppression, tumor inflammation, metabolism reprogramming, drug resistance, cancer stemness. Therefore...

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Bibliographic Details
Published in:Journal of experimental & clinical cancer research 2024-01, Vol.43 (1), p.23-23, Article 23
Main Authors: Hu, Yamei, Dong, Zigang, Liu, Kangdong
Format: Article
Language:English
Subjects:
Amino acids
Angiogenesis
Apoptosis
B cells
Cancer
Chemotherapy
Cytokines
Development and progression
Drug Discovery
Drug resistance
Growth factors
Health aspects
Humans
Immunosuppression
Immunosuppression Therapy
Immunotherapy
Inflammation
Inhibitors
Kinases
Leukemia
Ligands
Mediation
Medical research
Medicine, Experimental
Metabolic reprogramming
Metabolism
Metastasis
Modulators
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - pathology
Phosphorylation
Prostate cancer
Signal Transduction
STAT3
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - metabolism
Tumor Microenvironment
Tumors
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Summary:Signal transducer and activator of transcription 3 (STAT3) is a transcriptional factor involved in almost all cancer hallmark features including tumor proliferation, metastasis, angiogenesis, immunosuppression, tumor inflammation, metabolism reprogramming, drug resistance, cancer stemness. Therefore, STAT3 has become a promising therapeutic target in a wide range of cancers. This review focuses on the up-to-date knowledge of STAT3 signaling in cancer. We summarize both the positive and negative modulators of STAT3 together with the cancer hallmarks involving activities regulated by STAT3 and highlight its extremely sophisticated regulation on immunosuppression in tumor microenvironment and metabolic reprogramming. Direct and indirect inhibitors of STAT3 in preclinical and clinical studies also have been summarized and discussed. Additionally, we highlight and propose new strategies of targeting STAT3 and STAT3-based combinations with established chemotherapy, targeted therapy, immunotherapy and combination therapy. These efforts may provide new perspectives for STAT3-based target therapy in cancer.
ISSN:1756-9966
0392-9078
1756-9966
DOI:10.1186/s13046-024-02949-5