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Title: Multicellular Effects of STAT3 in Non-small Cell Lung Cancer: Mechanistic Insights and Therapeutic Opportunities.
Austin Authors: Parakh, Sagun ;Ernst, Matthias ;Poh, Ashleigh R
Affiliation: Olivia Newton-John Cancer Research Institute
School of Cancer Medicine, La Trobe University, Melbourne, VIC 3086, Australia
Issue Date: 11-Dec-2021 2021
Publication information: Cancers 2021; 13(24): 6228.
Abstract: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for 85% of lung cancer cases. Aberrant activation of the Signal Transducer and Activator of Transcription 3 (STAT3) is frequently observed in NSCLC and is associated with a poor prognosis. Pre-clinical studies have revealed an unequivocal role for tumor cell-intrinsic and extrinsic STAT3 signaling in NSCLC by promoting angiogenesis, cell survival, cancer cell stemness, drug resistance, and evasion of anti-tumor immunity. Several STAT3-targeting strategies have also been investigated in pre-clinical models, and include preventing upstream receptor/ligand interactions, promoting the degradation of STAT3 mRNA, and interfering with STAT3 DNA binding. In this review, we discuss the molecular and immunological mechanisms by which persistent STAT3 activation promotes NSCLC development, and the utility of STAT3 as a prognostic and predictive biomarker in NSCLC. We also provide a comprehensive update of STAT3-targeting therapies that are currently undergoing clinical evaluation, and discuss the challenges associated with these treatment modalities in human patients.
DOI: 10.3390/cancers13246228
ORCID: 0000-0003-3891-2489
Journal: Cancers
PubMed URL: 34944848
PubMed URL:
ISSN: 2072-6694
Type: Journal Article
Subjects: NSCLC
clinical trials
drug resistance
lung cancer
tumor microenvironment
tyrosine kinase inhibitors
Appears in Collections:Journal articles

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