[Lung cancers with rare oncogenic drivers: RET, ROS-1, MET, HER2 and BRAF]

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Non-small cell lung cancer (NSCLC) frequently presents with oncogenic drivers.
• Rare oncogenic drivers (<5% incidence), including ROS-1/RET rearrangements and MET/BRAF/HER2 mutations, are increasingly identified.
• Targeted therapies demonstrate superior tumor response and tolerability over chemotherapy in NSCLC.

Purpose of the Study:

• To review current targeted therapies for rare oncogenic drivers in NSCLC.
• To discuss emerging therapeutic molecules for these specific genetic alterations.
• To emphasize the importance of comprehensive driver screening for personalized medicine in NSCLC.

Main Methods:

• Literature review of targeted therapies and oncogenic drivers in NSCLC.
• Analysis of treatment efficacy and safety data for rare driver mutations.
• Discussion of therapeutic strategies available in France and future prospects.

Main Results:

• Targeted therapies show significant efficacy in NSCLC with oncogenic drivers, often outperforming chemotherapy.
• Immune checkpoint inhibitors may be less effective when oncogenic drivers are present.
• Targeted therapies are established as first-line treatments for ROS-1/RET alterations and second-line for MET/BRAF mutations.

Conclusions:

• Comprehensive screening for oncogenic drivers, including rare ones, is crucial at diagnosis for effective NSCLC management.
• Targeted therapies represent a cornerstone of personalized medicine, revolutionizing NSCLC treatment.
• Ongoing research into novel molecules promises further advancements for patients with rare oncogenic drivers.