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Updated: Apr 15, 2026
Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Molecular histology of lung cancer: from targets to treatments
Steven L Wood1, Maria Pernemalm2, Philip A Crosbie1
1Faculty Institute of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Wolfson Molecular Imaging Centre, Manchester M20 3LJ, UK.
Abstract:
Lung cancer is the leading cause of cancer-related death worldwide with a 5-year survival rate of less than 15%, despite significant advances in both diagnostic and therapeutic approaches. Combined genomic and transcriptomic sequencing studies have identified numerous genetic driver mutations that are responsible for the development of lung cancer. In addition, molecular profiling studies identify gene products and their mutations which predict tumour responses to targeted therapies such as protein tyrosine kinase inhibitors and also can offer explanation for drug resistance mechanisms. The profiling of circulating micro-RNAs has also provided an ability to discriminate patients in terms of prognosis/diagnosis and high-throughput DNA sequencing strategies are beginning to elucidate cell signalling pathway mutations associated with oncogenesis, including potential stem cell associated pathways, offering the promise that future therapies may target this sub-population, preventing disease relapse post treatment and improving patient survival. This review provides an assessment of molecular profiling within lung cancer concerning molecular mechanisms, treatment options and disease-progression. Current areas of development within lung cancer profiling are discussed (i.e. profiling of circulating tumour cells) and future challenges for lung cancer treatment addressed such as detection of micro-metastases and cancer stem cells.
Insights
Molecular profiling of lung cancer reveals genetic mutations driving disease and predicting treatment response. Future therapies may target cancer stem cells to prevent relapse and improve survival.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Lung cancer remains a leading cause of cancer death globally, with low survival rates despite treatment advances.
- Genomic and transcriptomic studies have identified key driver mutations in lung cancer development.
- Molecular profiling aids in predicting tumor response to targeted therapies and understanding drug resistance.
Purpose of the Study:
- To review molecular profiling in lung cancer, covering mechanisms, treatments, and progression.
- To discuss current advancements in lung cancer profiling, including circulating tumor cells.
- To address future challenges in lung cancer treatment, such as detecting micrometastases and cancer stem cells.
Main Methods:
- Review of combined genomic and transcriptomic sequencing studies.
- Analysis of molecular profiling data for targeted therapy prediction.
- Assessment of circulating micro-RNA and DNA sequencing strategies.
Main Results:
- Identification of genetic driver mutations and their role in lung cancer.
- Discovery of molecular markers for predicting response to targeted therapies like tyrosine kinase inhibitors.
- Circulating micro-RNAs show potential for patient prognosis and diagnosis.
Conclusions:
- Molecular profiling is crucial for understanding lung cancer mechanisms and guiding treatment.
- Emerging techniques like circulating tumor cell profiling offer new diagnostic and prognostic avenues.
- Targeting cancer stem cells and detecting micrometastases are key future challenges for improving patient survival.
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