Oncogenic alterations in advanced NSCLC: a molecular super-highway

Area of Science:

• Oncology and Molecular Biology
• Genetics and Genomics
• Pharmacology

Background:

• Lung cancer is a leading cause of cancer death globally, with non-small cell lung cancer (NSCLC) being the most common type.
• Recent decades have seen significant advancements in classifying NSCLC based on molecular oncogenic subsets, impacting prognosis and treatment.
• Targetable molecular alterations, such as EGFR, are now identified in a substantial percentage of lung adenocarcinoma patients, particularly in Asian populations.

Purpose of the Study:

• To review the current landscape of oncogenic driver alterations in advanced NSCLC.
• To discuss the diagnostic approaches and management strategies for NSCLC based on molecular profiling.
• To explore future perspectives and challenges in the field of precision medicine for lung cancer.

Main Methods:

• Review of current literature on molecular alterations in NSCLC.
• Discussion of diagnostic technologies, including next-generation sequencing (NGS).
• Analysis of targeted therapies and resistance mechanisms.

Main Results:

• Approximately 60-80% of lung adenocarcinoma patients harbor targetable molecular alterations.
• Key druggable targets include EGFR, ALK, BRAF, ROS1, KRAS, HER2, MET, NTRK, RET, and NRG1, with PI3K and FGFR also under investigation.
• Oncogenic drivers are more prevalent in non-smokers, East Asians, and younger patients.

Conclusions:

• Precision medicine, driven by molecular diagnostics like NGS, is crucial for personalized NSCLC treatment.
• Identifying oncogenic drivers allows for targeted therapy selection and management of resistance.
• Continued research is essential to overcome challenges and further refine lung cancer treatment strategies.