Dataset Information

Multicellular Effects of STAT3 in Non-small Cell Lung Cancer: Mechanistic Insights and Therapeutic Opportunities.

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.

SUBMITTER: Parakh S

PROVIDER: S-EPMC8699548 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multicellular Effects of STAT3 in Non-small Cell Lung Cancer: Mechanistic Insights and Therapeutic Opportunities.

Parakh Sagun S Ernst Matthias M Poh Ashleigh R AR

Cancers 20211211 24

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-tumo ...[more]

PMID: 34944848

Similar Datasets

Project description:Summary Background Women are at greater risk of developing non-small cell lung cancer (NSCLC), yet the underlying causes remain unclear. Methods We performed whole genome scans in lung tumours of cRaf transgenic mice and identified miRNA, transcription factor and hormone receptor dependent gene regulations. We confirmed hormone receptors by immunohistochemistry and constructed regulatory gene networks by considering experimentally validated miRNA-gene and transcription factor-miRNA/gene targets. Bioinformatics, genomic foot-printing and gene enrichment analysis established sex-specific circuits of lung tumour growth. Translational research involved a large cohort of NSCLC patients. We evaluated commonalities in sex-specific NSCLC gene regulations between mice and humans and determined their prognostic value in Kaplan–Meier survival statistics and COX proportional hazard regression analysis. Findings Overexpression of the cRaf kinase elicited an extraordinary 8-fold increase in tumour growth among females, and nearly 70% of the 112 differentially expressed genes (DEGs) were female specific. We identified oncogenes, oncomirs, tumour suppressors, cell cycle regulators and MAPK/EGFR signalling molecules, which prompted sex-based differences in NSCLC, and we deciphered a regulatory gene-network, which protected males from accelerated tumour growth. Strikingly, 41% of DEGs are targets of hormone receptors, and the majority (85%) are oestrogen receptor (ER) dependent. We confirmed the role of ER in a large cohort of NSCLC patients and validated 40% of DEGs induced by cRaf in clinical tumour samples. Interpretation We report the molecular wiring that prompted sex disparities in tumour growth. This allowed us to propose the development of molecular targeted therapies by jointly blocking ER, CDK1 and arginase 2 in NSCLC. Funding We gratefully acknowledge the financial support of the Lower Saxony Ministry of Culture and Sciences and Volkswagen Foundation, Germany to JB (25A.5-7251-99-3/00) and of the Chinese Scholarship Council to SZ (202008080022). This publication is funded by the Deutsche Forschungsgemeinschaft (DFG) as part of the “Open Access Publikationskosten” program.

Dataset Information

Multicellular Effects of STAT3 in Non-small Cell Lung Cancer: Mechanistic Insights and Therapeutic Opportunities.

Publications

Multicellular Effects of STAT3 in Non-small Cell Lung Cancer: Mechanistic Insights and Therapeutic Opportunities.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets