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

Ke Gong, Gao Guo, Nicole Beckley, Yue Zhang, Xiaoyao Yang, Mishu Sharma, Amyn A. Habib

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)189-196
Number of pages8
JournalNeoplasia (United States)
Volume23
Issue number2
DOIs
StatePublished - Feb 2021

Keywords

  • EGFR inhibition
  • Immunotherapy
  • NSCLC
  • TCGA
  • TNF
  • Therapeutic resistance

ASJC Scopus subject areas

  • Cancer Research

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