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Updated: May 12, 2026
Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Novel therapeutic targets in non-small cell lung cancer
Muhammad Alamgeer1, Vinod Ganju, D Neil Watkins
1Department of Medical Oncology, Monash Medical Centre, 823-865 Centre Road, East Bentleigh, Vic 3165, Australia.
Abstract:
Oncogenic driver mutations frequently occur in lung cancer and play role in carcinogenesis. These mutations are usually associated with distinct clinical and histological features and are attractive targets for anticancer therapy. Recently, several molecularly distinct phenotypes of NSCLC based on specific and mutually exclusive genetic derangements have been described. Few targets like epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with EGFR tyrosine kinase inhibitors (TKIs) and crizotinib, respectively. Many more inhibitors of specific driver mutations involving genes like ROS, c-MET, FGFR, mTOR, IGFR and RET are currently under development. However, efforts to target some mutated genes like K-RAS have been unsuccessful. Moreover, the emerging challenge of acquired resistance to initially effective therapy is becoming another major concern. In this review recent data on novel molecular targets and their future prospects are discussed.
Insights
Lung cancer treatment targets oncogenic driver mutations. While some therapies show success, challenges like resistance and targeting K-RAS mutations persist, necessitating novel molecular strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Oncogenic driver mutations are key in lung cancer development.
- Specific mutations define distinct non-small cell lung cancer (NSCLC) phenotypes.
- Targeting these mutations offers a promising therapeutic avenue.
Purpose of the Study:
- To review recent advancements in novel molecular targets for lung cancer.
- To discuss the future prospects of targeting specific genetic derangements.
- To highlight challenges including acquired resistance and targeting difficult mutations.
Main Methods:
- Literature review of recent data on molecular targets in lung cancer.
- Analysis of successful and unsuccessful targeted therapies.
- Discussion of emerging resistance mechanisms.
Main Results:
- Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are successfully targeted by tyrosine kinase inhibitors (TKIs) and crizotinib.
- Inhibitors for ROS, c-MET, FGFR, mTOR, IGFR, and RET are under development.
- Targeting K-RAS mutations remains challenging, and acquired resistance is a significant concern.
Conclusions:
- Targeted therapies based on specific oncogenic mutations have revolutionized lung cancer treatment.
- Ongoing research focuses on developing inhibitors for new targets and overcoming resistance.
- Future lung cancer therapy will likely involve a combination of targeted agents and strategies to manage resistance.
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