STAT3 as a potential therapeutic target in triple negative breast cancer: a systematic review

J Exp Clin Cancer Res. 2019 May 14;38(1):195. doi: 10.1186/s13046-019-1206-z.


Triple negative breast cancer (TNBC), which is typically lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), represents the most aggressive and mortal subtype of breast cancer. Currently, only a few treatment options are available for TNBC due to the absence of molecular targets, which underscores the need for developing novel therapeutic and preventive approaches for this disease. Recent evidence from clinical trials and preclinical studies has demonstrated a pivotal role of signal transducer and activator of transcription 3 (STAT3) in the initiation, progression, metastasis, and immune evasion of TNBC. STAT3 is overexpressed and constitutively activated in TNBC cells and contributes to cell survival, proliferation, cell cycle progression, anti-apoptosis, migration, invasion, angiogenesis, chemoresistance, immunosuppression, and stem cells self-renewal and differentiation by regulating the expression of its downstream target genes. STAT3 small molecule inhibitors have been developed and shown excellent anticancer activities in in vitro and in vivo models of TNBC. This review discusses the recent advances in the understanding of STAT3, with a focus on STAT3's oncogenic role in TNBC. The current targeting strategies and representative small molecule inhibitors of STAT3 are highlighted. We also propose potential strategies that can be further examined for developing more specific and effective inhibitors for TNBC prevention and therapy.

Keywords: Immune escape; Oncogene; STAT3; Small molecule inhibitors; Triple negative breast cancer.

Publication types

  • Systematic Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Biomarkers, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Molecular Targeted Therapy*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / metabolism
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / immunology
  • Oncogenes
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • Signal Transduction / drug effects*
  • Triple Negative Breast Neoplasms / drug therapy*
  • Triple Negative Breast Neoplasms / etiology
  • Triple Negative Breast Neoplasms / metabolism*
  • Tumor Escape / genetics
  • Tumor Escape / immunology


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • STAT3 Transcription Factor
  • STAT3 protein, human