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Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Targeted therapies for treatment of non-small cell lung cancer--Recent advances and future perspectives
Joan Minguet1,2, Katherine H Smith1, Peter Bramlage1,2
1European Institute of Cancer Research (EICR), Carrer Del Passeig, 2, Terrassa, 08221, Spain.
Abstract:
Non-small cell lung cancer (NSCLC) is one of the most deadly cancers worldwide, with poor prognosis once the disease has progressed past the point at which surgery is a viable option. Whilst chemotherapy has improved survival over recent decades, there is still great need for improvements in treatments for patients with advanced disease. Over the last decade, a variety of such drugs have received market approval for treating NSCLC, with a variety of others in the pipeline. Here, we review the development of targeted therapies for the treatment of advanced or metastatic NSCLC, including those already in clinical practice and those in early trials. The epidermal growth factor receptor (EGFR) inhibitors, gefitinib, erlotinib and afatinib; the anaplastic lymphoma kinase (ALK) inhibitor, crizotinib; and the anti-vascular endothelial growth factor receptor monoclonal antibody, bevacizumab, are already providing improved survival for patients with NSCLC. Moreover, the discovery of EGFR mutations and ALK rearrangements has enabled the identification of patients who are more likely to benefit from a specific drug. The recent approval of the immune checkpoint inhibitor nivolumab, along with the designation of alectinib and MPDL3280A as breakthrough therapies by the FDA, demonstrates how rapidly this area of research is expanding. Over the last decade there has been significant progress made in the treatment of advanced NSCLC, and the large and varied selection of drugs currently undergoing trials provide great promise for improving the prognosis of this highly prevalent and deadly form of cancer.
Insights
Targeted therapies and immune checkpoint inhibitors are improving survival for advanced non-small cell lung cancer (NSCLC). Ongoing research and drug development offer significant promise for better patient outcomes in this deadly disease.
Area of Science:
- Oncology
- Pharmacology
- Cancer Research
Background:
- Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality worldwide.
- Prognosis is particularly poor for patients with advanced or metastatic disease.
- Existing chemotherapy treatments offer limited efficacy for advanced NSCLC.
Purpose of the Study:
- To review the development of targeted therapies for advanced or metastatic NSCLC.
- To highlight approved and investigational drugs in clinical practice and early trials.
- To discuss the impact of identifying specific genetic mutations and rearrangements for personalized treatment.
Main Methods:
- Review of clinical data and research on targeted therapies for NSCLC.
- Analysis of approved drugs including EGFR inhibitors (gefitinib, erlotinib, afatinib), ALK inhibitor (crizotinib), and anti-VEGFR antibody (bevacizumab).
- Examination of emerging immunotherapies like immune checkpoint inhibitors (nivolumab, alectinib, MPDL3280A).
Main Results:
- Targeted therapies such as EGFR and ALK inhibitors have demonstrated improved survival rates in NSCLC patients.
- Identification of EGFR mutations and ALK rearrangements allows for patient stratification and personalized treatment.
- Recent approvals and designations of novel immunotherapies signify rapid advancements in NSCLC treatment.
Conclusions:
- Significant progress has been made in treating advanced NSCLC over the past decade.
- A growing pipeline of diverse targeted therapies and immunotherapies offers substantial promise for improving patient prognosis.
- Personalized medicine approaches based on molecular profiling are transforming NSCLC treatment paradigms.
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