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

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Tumor necrosis factor (TNF) and its receptors are prevalent in non-small cell lung cancer (NSCLC).
• TNF is implicated in inflammation-induced carcinogenesis and can exhibit both pro- and anti-tumorigenic effects.
• NF-κB is a critical transcription factor activated by TNF, playing a key role in inflammation and cancer.

Purpose of the Study:

• To elucidate the complex role of TNF and its receptors in NSCLC.
• To investigate TNF's involvement in resistance to epidermal growth factor receptor (EGFR) inhibitors.
• To explore the potential of TNF inhibitors in combination therapies for NSCLC.

Main Methods:

• Analysis of The Cancer Genome Atlas database for TNF as a potential NSCLC biomarker.
• Review of recent studies on TNF upregulation in response to EGFR inhibition.
• Examination of experimental models combining EGFR and TNF inhibition.

Main Results:

• TNF upregulation and subsequent NF-κB activation are observed in NSCLC treated with EGFR inhibitors.
• This TNF/NF-κB pathway contributes to primary and secondary resistance to EGFR inhibition.
• Combined inhibition of EGFR and TNF demonstrated efficacy in overcoming therapeutic resistance in experimental models.
• TNF may also influence immunotherapy toxicity and resistance to immune checkpoint inhibitors.

Conclusions:

• TNF has a complex, often oncogenic, role in NSCLC, particularly in mediating resistance to targeted therapies.
• Targeting TNF in combination with EGFR inhibitors offers a promising strategy to overcome therapeutic resistance in NSCLC.
• TNF inhibitors, already used for inflammatory diseases, could be valuable in NSCLC treatment regimens.