Current status of molecular diagnostics for lung cancer

Area of Science:

• Oncology
• Molecular Diagnostics
• Genetics

Background:

• Lung cancer (LC) management necessitates analyzing diverse molecular targets like oncogene mutations and gene fusions.
• Immune checkpoint inhibitors (ICIs) administration relies on PD-L1 expression and tumor mutation burden (TMB) assessment.
• Patient clinical characteristics, including age, gender, and smoking history, impact the prevalence of specific molecular targets in LC.

Purpose of the Study:

• To outline the spectrum of molecular targets crucial for lung cancer management.
• To highlight the role of clinical characteristics in predicting targetable alterations.
• To emphasize the need for rapid molecular testing and the growing importance of RNA next-generation sequencing (NGS).

Main Methods:

• Analysis of kinase activating mutations (EGFR, ERBB2, BRAF, MET).
• Detection of KRAS G12C substitutions.
• Identification of gene fusions (ALK, ROS1, RET, NTRK1-3).
• Immunohistochemical (IHC) analysis of PD-L1 expression.
• Determination of tumor mutation burden (TMB).
• RNA next-generation sequencing (NGS) for comprehensive molecular profiling.

Main Results:

• Specific patient demographics correlate with distinct molecular alterations (e.g., young patients with kinase rearrangements, smokers with KRAS G12C/high TMB).
• Timely completion of molecular tests (within 10 working days) is critical for optimal first-line therapy selection.
• RNA-based NGS demonstrates capability in detecting the full range of actionable genomic alterations in lung cancer.

Conclusions:

• Comprehensive molecular profiling is essential for guiding lung cancer treatment decisions.
• RNA-based NGS is increasingly the preferred method for molecular diagnosis due to its ability to detect multiple targetable alterations.
• Integrating clinical information with molecular data enhances the precision of lung cancer management.