Molecular Targets in Non-Small Cell Lung Cancer
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Updated: Feb 17, 2026
Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Ryan Griffin1,2, Robert A Ramirez1,2
1Department of Hematology/Oncology, Ochsner Clinic Foundation, New Orleans, LA.
Background:
Lung cancer is the second most common cancer in the United States among men and women, and it is the most common cause of cancer-related death. Non-small cell lung cancer (NSCLC) represents approximately 85% of all lung cancer cases. Historically, patients with metastatic NSCLC received similar cytotoxic chemotherapy regimens. Genotyping studies have revealed genetic/molecular abnormalities in lung cancer. These driver mutations render a cancer dependent on that specific mutation's biochemical pathway for its growth and survival. With the development of tyrosine kinase inhibitors and antibodies against specific driver mutations, the landscape of lung cancer treatment has changed from treatment based on histologic subtype to treatment based on molecularly defined subtypes.
Methods:
In this article, we review the current molecular-targeted therapies in lung cancer.
Results:
We review landmark trials that have led to approval of molecular-targeted therapies against epidermal growth factor receptor, anaplastic lymphoma kinase, and ROS1. We also explore less common mutations/molecular abnormalities and review data on the use of targeted therapies against them. Finally, we offer a treatment algorithm for patients with metastatic NSCLC that harbors actionable mutations.
Conclusion:
Patients with advanced NSCLC should undergo mutational testing to evaluate for actionable mutations. If such a mutation is discovered, targeted therapy should be considered for first-line treatment.
Insights
Molecular testing for lung cancer patients with advanced non-small cell lung cancer (NSCLC) is crucial. Identifying actionable mutations can guide first-line targeted therapy, improving treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer is a leading cause of cancer death, with non-small cell lung cancer (NSCLC) comprising 85% of cases.
- Traditional treatment relied on chemotherapy, but driver mutations have shifted focus to molecularly targeted therapies.
- Understanding genetic abnormalities is key to personalized lung cancer treatment.
Purpose of the Study:
- To review current molecular-targeted therapies for lung cancer.
- To discuss landmark trials and approved targeted treatments.
- To provide a treatment algorithm for metastatic NSCLC with actionable mutations.
Main Methods:
- Review of landmark clinical trials for targeted therapies.
- Exploration of less common mutations and their targeted treatments.
- Development of a treatment algorithm based on molecular profiling.
Main Results:
- Landmark trials support targeted therapies for EGFR, ALK, and ROS1 mutations.
- Data on targeted therapies for less common mutations are reviewed.
- A treatment algorithm for metastatic NSCLC with actionable mutations is presented.
Conclusions:
- Mutational testing is recommended for advanced NSCLC patients.
- Actionable mutations should be identified to guide treatment decisions.
- Targeted therapy should be considered as first-line treatment when actionable mutations are found.
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