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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Advances in Targeted Therapy for Non-Small-Cell Lung Cancer: Current Progress and Future Directions
Supriya Peshin1, Ehab Takrori2, Joseph H Yazji3
1Department of Internal Medicine, Norton Community Hospital, Norton, VA 24273, USA.
Abstract:
The advent of targeted therapies has significantly transformed the management of non-small-cell lung cancer (NSCLC), improving survival across all disease stages. Discoveries of both common and rare oncogenic drivers are advancing rapidly, posing a challenge for clinicians and researchers to remain up to date in this dynamic field. This review highlights the evolving landscape of therapeutic strategies for actionable mutations in lung cancer, with particular attention given to the latest developments in KRAS-targeted treatments including non-G12C mutations, pan-RAS inhibitors, and agents targeting RAS-GTP. We also examine the existing standards of care for NSCLC harboring EGFR and ALK alterations, as well as emerging therapies poised for clinical use. Additional discussion includes advancements in therapies directed at MET, HER2, RET, ROS1, and FGFR alterations-each representing promising targets in NSCLC. This review concludes by exploring the growing evidence surrounding TROP-2 as a novel therapeutic target, especially relevant in cases where previous targeted treatments have failed.
Insights
Targeted therapies are revolutionizing non-small-cell lung cancer (NSCLC) treatment by targeting specific mutations. This review details advancements in KRAS, EGFR, ALK, and other actionable targets, offering new hope for patients.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Targeted therapies have transformed non-small-cell lung cancer (NSCLC) management, improving survival.
- Rapid discoveries of oncogenic drivers necessitate continuous updates in clinical practice.
- Actionable mutations present opportunities for personalized treatment strategies in NSCLC.
Purpose of the Study:
- To review the evolving landscape of targeted therapies for actionable mutations in NSCLC.
- To highlight recent advancements in KRAS-targeted treatments, including non-G12C mutations and pan-RAS inhibitors.
- To discuss emerging therapies for EGFR, ALK, MET, HER2, RET, ROS1, FGFR, and TROP-2 alterations.
Main Methods:
- Literature review of recent clinical trials and research publications.
- Analysis of therapeutic strategies for specific oncogenic drivers in NSCLC.
- Synthesis of information on established and novel targeted agents.
Main Results:
- Significant progress in KRAS-targeted therapies, including non-G12C and pan-RAS inhibitors.
- Established standards of care for EGFR and ALK alterations continue to evolve.
- Emerging therapies for MET, HER2, RET, ROS1, FGFR, and TROP-2 show promise.
Conclusions:
- The field of targeted therapy for NSCLC is rapidly advancing, offering more treatment options.
- KRAS and TROP-2 represent key areas of recent development.
- Personalized medicine approaches are crucial for optimizing NSCLC patient outcomes.
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