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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Recent Progress in Rare Oncogenic Drivers and Targeted Therapy For Non-Small Cell Lung Cancer
Yijia Guo1, Rui Cao1, Xiangyan Zhang1
1Department of Oncology, Shengjing Hospital of China Medical University, China Medical University, Shenyang, People's Republic of China.
Abstract:
Non-small cell lung cancer (NSCLC) is frequently associated with oncogenic driver mutations, which play an important role in carcinogenesis and cancer progression. Targeting epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase rearrangements has become standard therapy for patients with these aberrations because of the greater improvement of survival, tolerance, and quality-of-life compared to chemotherapy. Clinical trials for emerging therapies that target other less common driver genes are generating mixed results. Here, we review the literature on rare drivers in NSCLC with frequencies lower than 5% (e.g., ROS1, RET, MET, BRAF, NTRK, HER2, NRG1, FGFR1, PIK3CA, DDR2, and EGFR exon 20 insertions). In summary, targeting rare oncogenic drivers in NSCLC has achieved some success. With the development of new inhibitors that target these rare drivers, the spectrum of targeted therapy has been expanded, although acquired resistance is still an unavoidable problem.
Insights
Targeting rare oncogenic driver mutations in non-small cell lung cancer (NSCLC) shows promise, expanding treatment options beyond common mutations. However, acquired resistance remains a significant challenge in these targeted therapies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Non-small cell lung cancer (NSCLC) is driven by oncogenic mutations.
- Targeting common mutations like EGFR and ALK rearrangements improves outcomes.
- Emerging therapies for rare drivers show variable results.
Purpose of the Study:
- To review literature on rare oncogenic drivers in NSCLC (frequency <5%).
- To summarize the efficacy and challenges of targeting these rare drivers.
Main Methods:
- Literature review of studies on rare NSCLC drivers.
- Analysis of clinical trial data for emerging targeted therapies.
Main Results:
- Targeted therapies for rare drivers (ROS1, RET, MET, BRAF, NTRK, HER2, NRG1, FGFR1, PIK3CA, DDR2, EGFR exon 20 insertions) have shown some success.
- Development of new inhibitors expands targeted therapy options.
- Acquired resistance is a persistent issue.
Conclusions:
- Targeting rare oncogenic drivers in NSCLC offers new therapeutic avenues.
- Continued development of novel inhibitors is crucial.
- Addressing acquired resistance is essential for long-term treatment efficacy.
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