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Novel activators and small-molecule inhibitors of STAT3 in cancer

Lehe Yang1, Shichong Lin2, Lingyuan Xu2

  • 1Department of Respiratory Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, University Town, Wenzhou, Zhejiang 325035, China; Department of Biochemistry and Molecular Biology, School of Medicine, University of Maryland, Baltimore, MD 21201, USA.

Cytokine & Growth Factor Reviews
|November 4, 2019
PubMed

Insights

Signal transducer and activator of transcription 3 (STAT3) is a promising cancer target, but clinical trials show mixed results. This review explores STAT3 activation mechanisms and small molecule inhibitors for cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Aberrant signal transducer and activator of transcription 3 (STAT3) signaling is implicated in numerous cancers.
  • Activated STAT3 presents a promising therapeutic target, with extensive preclinical and clinical investigation.
  • Targeting STAT3 in cancer has yielded complex and varied outcomes in early clinical trials.

Purpose of the Study:

  • To review the diverse mechanisms driving oncogenic STAT3 activation.
  • To discuss small molecule inhibitors targeting STAT3 in cancer therapy.
  • To provide insights into the complexities of STAT3-targeted cancer treatments.

Main Methods:

  • Literature review of preclinical and clinical studies on STAT3 signaling in cancer.
  • Analysis of mechanisms underlying STAT3 oncogenic activation.
  • Examination of small molecule inhibitors designed to target STAT3.

Main Results:

  • STAT3 activation occurs through multiple oncogenic pathways.
  • Various small molecule inhibitors targeting STAT3 have been developed.
  • Clinical efficacy of STAT3 inhibitors is influenced by pathway complexity and tumor heterogeneity.

Conclusions:

  • STAT3 remains a significant target in oncology, despite therapeutic challenges.
  • Understanding diverse STAT3 activation mechanisms is crucial for effective drug development.
  • Further research is needed to optimize STAT3-targeted therapies for improved cancer treatment outcomes.
Keywords:
ActivatorCancerInhibitorSTAT3Signal pathway

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