Related Experiment Video
Updated: Dec 17, 2025
Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Molecular therapeutic targets in non-small cell lung cancer
Kamya Sankar1, Shirish M Gadgeel2, Angel Qin1
1University of Michigan , Ann Arbor, MI, USA.
Introduction:
Several targetable genetic alterations have been identified in non-small cell lung cancers (NSCLC) and drugs targeting these alterations have been approved for the management of advanced NSCLC patients. Driver mutations with emerging clinical trial data include EGFR exon 20 insertion mutations, MET amplification, KRAS G12 C point mutations, RET rearrangements, HER2 amplification and mutations, and FGFR amplification and translocations.
Areas Covered:
We reviewed English-language articles indexed in Medline and PubMed up to the 1st of June 2020. In addition, the proceedings of major conferences were reviewed for relevant abstracts. We report data published regarding targeted therapies which are currently approved and for those which are emerging in advanced or metastatic NSCLC.
Expert Review:
While these drugs have been shown to be efficacious and tolerable, resistance almost always develops. Though next-generation tyrosine kinase inhibitors (TKIs) have been developed, the appropriate sequencing of these drugs is not clear. Evaluating combination therapies to prevent or delay the onset of resistance and understanding mechanisms of resistance are critical areas of emerging research.
Insights
Targeted therapies for non-small cell lung cancer (NSCLC) show promise, but drug resistance is a significant challenge. Research is focusing on combination therapies and understanding resistance mechanisms to improve patient outcomes.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Non-small cell lung cancer (NSCLC) has several targetable genetic alterations.
- Approved drugs exist for advanced NSCLC patients with specific mutations.
Purpose of the Study:
- To review approved and emerging targeted therapies for advanced or metastatic NSCLC.
- To highlight key genetic alterations and their targeted treatments.
Main Methods:
- Comprehensive literature review of Medline and PubMed up to June 2020.
- Inclusion of major conference proceedings for relevant abstracts.
Main Results:
- Identified targetable alterations including EGFR, MET, KRAS, RET, HER2, and FGFR.
- Reviewed approved and emerging targeted therapies for these alterations.
Conclusions:
- Drug resistance is a major challenge in targeted NSCLC therapy.
- Further research into combination therapies and resistance mechanisms is critical.
- Optimal sequencing of next-generation tyrosine kinase inhibitors (TKIs) requires further investigation.
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