A Functional Genomics Review of Non-Small-Cell Lung Cancer in Never Smokers

Area of Science:

• Oncology
• Genomics
• Molecular Biology

Background:

• Lung cancer in never smokers (LCINS) is under-researched, despite distinct genomic profiles compared to smokers.
• Differences in somatic mutations, tumor mutational burden, and chromosomal aberrations suggest LCINS is a separate disease entity.
• Existing treatments and outcomes vary between never smokers and smokers with non-small cell lung cancer (NSCLC).

Purpose of the Study:

• To review actionable driver alterations and the genomic landscape in LCINS.
• To explore the genetic and environmental factors contributing to LCINS development.
• To identify novel molecular targets for improved LCINS treatment outcomes.

Main Methods:

• Literature review of driver genes and pathways in LCINS pathogenesis.
• Exploration of the genomic landscape and tumor microenvironment in LCINS.
• Analysis of genetic and environmental aspects of lung cancer in never smokers.

Main Results:

• Epidermal growth factor receptor (EGFR) mutations and EML4-ALK rearrangements are more frequent in never smokers.
• Never smokers with NSCLC may exhibit resistance to chemotherapy and reduced benefit from PD-L1 immune therapies.
• Genomic and epigenomic underpinnings of LCINS require further elucidation.

Conclusions:

• A deeper understanding of LCINS genomics is essential for developing novel targeted therapies.
• Defining genetic and environmental factors is critical for advancing lung cancer research in never smokers.
• Tailored therapeutic strategies are needed for LCINS to improve patient outcomes.