Fusion-positive non-small cell lung carcinoma: Biological principles, clinical practice, and diagnostic implications
Daniel Kazdal1,2,3, Véronique Hofman4,5,6, Petros Christopoulos2,3,7
1Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
Abstract:
Based on superior efficacy and tolerability, targeted therapy is currently preferred over chemotherapy and/or immunotherapy for actionable gene fusions that occur in late-stage non-small cell lung carcinoma (NSCLC). Consequently, current clinical practice guidelines mandate testing for ALK, ROS1, NTRK, and RET gene fusions in all patients with newly diagnosed advanced non-squamous NSCLC (NS-NSCLC). Gene fusions can be detected using different approaches, but today RNA next-generation sequencing (NGS) or combined DNA/RNA NGS is the method of choice. The discovery of other gene fusions (involving, eg, NRG1, NUT, FGFR1, FGFR2, MET, BRAF, EGFR, SMARC fusions) and their partners has increased progressively in recent years, leading to the development of new and promising therapies and mandating the development and implementation of comprehensive detection methods. The purpose of this review is to focus on recent data concerning the main gene fusions identified in NSCLC, followed by the discussion of major challenges in this domain.
Insights
Targeted therapy is preferred for advanced non-small cell lung cancer (NSCLC) with actionable gene fusions. RNA next-generation sequencing (NGS) is the preferred detection method, with ongoing discovery of new fusions and therapies.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Targeted therapy shows superior efficacy and tolerability compared to traditional treatments for advanced non-small cell lung carcinoma (NSCLC) with actionable gene fusions.
- Clinical guidelines recommend testing for specific gene fusions (ALK, ROS1, NTRK, RET) in newly diagnosed advanced non-squamous NSCLC (NS-NSCLC).
Purpose of the Study:
- To review recent data on major gene fusions identified in NSCLC.
- To discuss the challenges associated with the detection of these gene fusions.
Main Methods:
- RNA next-generation sequencing (NGS) or combined DNA/RNA NGS is the current gold standard for detecting gene fusions.
- Review of recent scientific literature on gene fusions in NSCLC.
Main Results:
- The discovery of additional gene fusions (e.g., NRG1, NUT, FGFR, MET, BRAF, EGFR, SMARC) and their partners is rapidly increasing.
- These discoveries are driving the development of novel and promising therapeutic strategies.
Conclusions:
- Comprehensive detection methods for a wider range of gene fusions are essential.
- Advances in understanding NSCLC molecular landscape are crucial for personalized treatment approaches.
