Tumor necrosis factor in lung cancer: Complex roles in biology and resistance to treatment.

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Abstrakt

Tytuł:: Tumor necrosis factor in lung cancer: Complex roles in biology and resistance to treatment.
Autorzy:: Gong K; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: .
Guo G; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Beckley N; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Zhang Y; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Yang X; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Sharma M; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Habib AA; Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; VA North Texas Health Care System, Dallas, TX, USA. Electronic address: .
Źródło:: Neoplasia (New York, N.Y.) [Neoplasia] 2021 Feb; Vol. 23 (2), pp. 189-196. Date of Electronic Publication: 2020 Dec 26.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Review
Język:: English
Imprint Name(s):: Publication: 2014- : [Amsterdam] : Elsevier
Original Publication: New York, NY : Stockton Press, c1999-
MeSH Terms:: Disease Susceptibility*
Lung Neoplasms/*etiology
Lung Neoplasms/*metabolism
Tumor Necrosis Factors/*metabolism
Animals ; Biomarkers ; Biomarkers, Tumor ; Disease Management ; Drug Resistance, Neoplasm/drug effects ; Drug Resistance, Neoplasm/genetics ; Gene Expression Regulation, Neoplastic ; Genomics/methods ; Humans ; Lung Neoplasms/pathology ; Lung Neoplasms/therapy ; Molecular Targeted Therapy ; NF-kappa B/metabolism ; Prognosis ; Treatment Outcome ; Tumor Necrosis Factors/genetics
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Grant Information:: I01 BX002559 United States BX BLRD VA; R01 CA244212 United States CA NCI NIH HHS
Contributed Indexing:: Keywords: EGFR inhibition; Immunotherapy; NSCLC; TCGA; TNF; Therapeutic resistance
Molecular Sequence:: ClinicalTrials.gov NCT00410059
Substance Nomenclature:: 0 (Biomarkers)
0 (Biomarkers, Tumor)
0 (NF-kappa B)
0 (Tumor Necrosis Factors)
Entry Date(s):: Date Created: 20201229 Date Completed: 20211012 Latest Revision: 20240330
Update Code:: 20240330
PubMed Central ID:: PMC7773536
DOI:: 10.1016/j.neo.2020.12.006
PMID:: 33373873
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Tumor necrosis factor (TNF) and its receptors are widely expressed in non-small cell lung cancer (NSCLC). TNF has an established role in inflammation and also plays a key role in inflammation-induced cancer. TNF can induce cell death in cancer cells and has been used as a treatment in certain types of cancer. However, TNF is likely to play an oncogenic role in multiple types of cancer, including NSCLC. TNF is a key activator of the transcription factor NF-κB. NF-κB, in turn, is a key effector of TNF in inflammation-induced cancer. Data from The Cancer Genome Atlas database suggest that TNF could be a biomarker in NSCLC and indicate a complex role for TNF and its receptors in NSCLC. Recent studies have reported that TNF is rapidly upregulated in NSCLC in response to targeted treatment with epidermal growth factor receptor (EGFR) inhibition, and this upregulation leads to NF-κB activation. The TNF upregulation and consequent NF-κB activation play a key role in mediating both primary and secondary resistance to EGFR inhibition in NSCLC, and a combined inhibition of EGFR and TNF can overcome therapeutic resistance in experimental models. TNF may mediate the toxic side effects of immunotherapy and may also modulate resistance to immune checkpoint inhibitors. Drugs inhibiting TNF are widely used for the treatment of various inflammatory and rheumatologic diseases and could be quite useful in combination with targeted therapy of NSCLC and other cancers.
(Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

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