STK11 as an Emerging Biomarker in Non-Small Cell Lung Cancer.

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genomics

Background:

• Immune checkpoint inhibitors (ICIs) have revolutionized non-small cell lung cancer (NSCLC) therapy, but only a fraction of patients achieve durable responses.
• Serine/threonine kinase 11 (STK11) mutations are emerging as critical biomarkers, associated with poor prognosis and resistance to ICIs in NSCLC.

Purpose of the Study:

• To review the function of STK11 in tumor biology.
• To highlight the prognostic and predictive significance of STK11 mutations in NSCLC treatment.
• To summarize emerging therapeutic strategies for STK11-mutant NSCLC.

Main Methods:

• Literature review of STK11 function, mutation co-occurrence, and clinical outcomes in NSCLC.
• Analysis of STK11's impact on tumor metabolism, angiogenesis, and immune evasion.
• Synthesis of data on ICI and targeted therapy efficacy in STK11-mutant NSCLC.

Main Results:

• STK11 loss disrupts AMPK/mTOR signaling, promoting tumor progression and immune evasion.
• STK11 mutations frequently co-occur with KRAS and KEAP1 alterations, correlating with low PD-L1 expression and resistance to PD-1/PD-L1 therapy.
• Inferior outcomes are consistently observed with ICIs and KRAS G12C inhibitors in STK11-mutant NSCLC, especially with KEAP1 co-mutations.

Conclusions:

• STK11 mutations are significant negative predictors of response to current immunotherapies and targeted therapies in NSCLC.
• Dual checkpoint inhibition shows potential but requires further investigation.
• Further research into novel treatment strategies is essential for improving outcomes in STK11-mutant NSCLC.