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Diagnosis and Treatment of ALK Aberrations in Metastatic NSCLC
Alex Friedlaender1, Giuseppe Banna2, Sandip Patel3
1Oncology Department, Geneva University Hospital (CH), Rue Gabrielle-Perret-Gentil 4, 1205, Genève, Switzerland.
Opinion Statement:
There has been rapid progress in the use of targeted therapies for ALK-positive which has led to improve dramatically PFS and OS in the metastatic ALK-rearranged NSCLC patients. There are several molecules now available (crizotinib, ceritinib, brigatinib, alectinib, and lorlatinib) and others in development. Such an improvement in treatment efficacy has even more highlighted the importance of an adequate identification of ALK alterations. Efficient and easily accessible testing tools are required to identify eligible patients in a timely fashion. Different methods for detecting ALK+ NSCLC patients are now available, with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) currently representing validated diagnostic techniques for the initial assessment of ALK status. Furthermore the widespread use of next-generation sequencing to detect other possible different activating mutations has allowed to identify individual ALK fusion variants. Several more expensive and time-consuming methods are also available nowadays which have the advantage to detect even rarer uncommon ALK fusion variants and mutations in tumour or blood samples. A review of the evolving testing-treatment landscape is needed to highlight the importance of properly diagnosing and treating this group of patients.
Insights
Targeted therapies have significantly improved outcomes for patients with ALK-positive metastatic non-small cell lung cancer (NSCLC). Accurate ALK alteration identification through advanced testing is crucial for timely and effective treatment selection.
Area of Science:
- Oncology
- Molecular Diagnostics
- Genetics
Background:
- Targeted therapies have revolutionized treatment for ALK-positive metastatic non-small cell lung cancer (NSCLC).
- Significant improvements in progression-free survival (PFS) and overall survival (OS) have been observed.
- The development of multiple ALK inhibitors (crizotinib, ceritinib, brigatinib, alectinib, lorlatinib) underscores treatment advancements.
Purpose of the Study:
- To review the evolving landscape of diagnostic testing for ALK alterations in NSCLC.
- To emphasize the critical role of accurate patient identification for targeted therapy selection.
- To highlight the importance of timely diagnosis and treatment for ALK-positive NSCLC.
Main Methods:
- Review of current diagnostic techniques for ALK alterations.
- Discussion of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) as validated methods.
- Exploration of next-generation sequencing (NGS) for identifying ALK fusion variants and uncommon mutations.
Main Results:
- FISH and IHC are established methods for initial ALK status assessment.
- NGS enables detection of diverse ALK fusion variants and mutations.
- Advanced methods can identify rare ALK alterations in tumor or blood samples.
Conclusions:
- Accurate and accessible ALK testing is paramount for optimizing targeted therapy in NSCLC.
- The choice of diagnostic method should align with the need to identify specific ALK alterations.
- A comprehensive understanding of the testing-treatment paradigm is essential for managing ALK-positive NSCLC patients.
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