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Structure, function, signaling pathways and clinical therapeutics: The translational potential of STAT3 as a target

Dandan Shi1, Jiejing Tao1, Shuli Man1

  • 1State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Microbiology, Ministry of Education, Tianjin Key Laboratory of Industry Microbiology, National and Local United Engineering Lab of Metabolic Control Fermentation Technology, China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, China.

Biochimica Et Biophysica Acta. Reviews on Cancer
|November 5, 2024
PubMed

Insights

Signal transducers and transcriptional activators 3 (STAT3) protein is overexpressed in many cancers, driving tumor growth and progression. Inhibiting STAT3 offers a promising therapeutic strategy for various cancer types.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Signal transducers and transcriptional activators 3 (STAT3) protein is frequently overexpressed in diverse cancer types.
  • STAT3 hyperactivation correlates with poor patient survival, highlighting its critical role in cancer progression.

Purpose of the Study:

  • To review the molecular mechanisms underlying STAT3's role in cancer development.
  • To summarize current direct and indirect STAT3 inhibitors in clinical studies.

Main Methods:

  • Literature review of STAT3's molecular functions in cancer.
  • Analysis of STAT3 activation pathways and downstream effects.
  • Summary of clinical trial data for STAT3 inhibitors.

Main Results:

  • STAT3 activation involves cytoplasmic signaling, nuclear enzyme interactions, and mitochondrial/endoplasmic reticulum roles.
  • Phosphorylated STAT3 (YP-STAT3) regulates angiogenesis, migration, proliferation, and stemness.
  • Phosphorylated STAT3 (SP-STAT3) impacts mitochondrial respiration, apoptosis, and calcium flux, influencing tumor progression.

Conclusions:

  • STAT3 is a key mediator of multiple cancer hallmarks.
  • Targeting STAT3, with agents like TTI101 and BBI608, presents a viable therapeutic avenue for cancer treatment.
Keywords:
CancerOrganelleSignal transducer and activator of transcription 3Signaling pathwayTargeted therapy

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