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Updated: Jul 16, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Path Less Traveled: Targeting Rare Driver Oncogenes in Non-Small-Cell Lung Cancer
Sun Min Lim1, Jii Bum Lee1, Yuko Oya2
1Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Abstract:
Over the past decade, tremendous efforts have been made in the development of targeted agents in non-small-cell lung cancer (NSCLC) with nonsquamous histology. Pivotal studies have used next-generation sequencing to select the patient population harboring oncogenic driver alterations that are targetable with targeted therapies. As treatment paradigm rapidly evolves for patients with rare oncogene-driven NSCLC, updated comprehensive overview of diagnostic approach and treatment options is paramount in clinical settings. In this review article, we discuss the epidemiology, molecular testing, and landmark clinical trials addressing the targeted agents for ROS1 rearrangement, METex14 skipping mutation, EGFR exon 20 insertion, KRAS G12C mutation, HER2 mutation, RET fusion, NTRK fusion, and BRAF mutations.
Insights
Targeted therapies are revolutionizing non-small-cell lung cancer (NSCLC) treatment for patients with specific genetic mutations. This review covers diagnostic approaches and landmark trials for rare oncogene-driven NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small-cell lung cancer (NSCLC) with nonsquamous histology has seen significant advancements in targeted therapy development over the last decade.
- Next-generation sequencing (NGS) is crucial for identifying oncogenic driver alterations amenable to targeted treatments.
Purpose of the Study:
- To provide a comprehensive overview of the diagnostic approach and treatment options for rare oncogene-driven NSCLC.
- To review landmark clinical trials for targeted agents against specific genetic alterations in NSCLC.
Main Methods:
- Literature review of pivotal studies and clinical trials.
- Focus on molecular testing strategies, including NGS.
- Analysis of targeted agents for specific mutations and fusions.
Main Results:
- Identification of key oncogenic driver alterations in NSCLC, including ROS1, METex14, EGFR exon 20, KRAS G12C, HER2, RET, NTRK, and BRAF.
- Overview of the efficacy and safety of targeted therapies for these alterations.
- Discussion of the evolving treatment landscape for rare oncogene-driven NSCLC.
Conclusions:
- Targeted therapies have transformed the treatment of NSCLC with specific driver mutations.
- Accurate molecular profiling is essential for selecting appropriate patients for targeted agents.
- Continued research and clinical trials are vital to further refine treatment strategies for rare oncogene-driven NSCLC.
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