Related Experiment Video
Updated: Apr 27, 2026
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
ALK-rearrangements and testing methods in non-small cell lung cancer: a review
Rodney E Shackelford1, Moiz Vora1, Kim Mayhall2
1LSU Health Shreveport, Department of Pathology, Shreveport, LA, USA.
Abstract:
The anaplastic lymphoma tyrosine kinase (ALK) gene was first described as a driver mutation in anaplastic non-Hodgkin's lymphoma. Dysregulated ALK expression is now an identified driver mutation in nearly twenty different human malignancies, including 4-9% of non-small cell lung cancers (NSCLC). The tyrosine kinase inhibitor crizotinib is more effective than standard chemotherapeutic agents in treating ALK positive NSCLC, making molecular diagnostic testing for dysregulated ALK expression a necessary step in identifying optimal treatment modalities. Here we review ALKmediated signal transduction pathways and compare the molecular protocols used to identify dysregulated ALK expression in NSCLC. We also discuss the use of crizotinib and second generation ALK tyrosine kinase inhibitors in the treatment of ALK positive NSCLC, and the known mechanisms of crizotinib resistance in NSCLC.
Insights
Anaplastic lymphoma kinase (ALK) gene mutations drive several cancers, including non-small cell lung cancer (NSCLC). Testing for ALK-positive NSCLC is crucial for effective treatment with targeted therapies like crizotinib.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Anaplastic lymphoma kinase (ALK) gene alterations are key drivers in various human cancers.
- Dysregulated ALK expression is identified in 4-9% of non-small cell lung cancer (NSCLC) cases.
- ALK-positive NSCLC patients show improved outcomes with crizotinib compared to standard chemotherapy.
Purpose of the Study:
- To review ALK-mediated signal transduction pathways.
- To compare molecular diagnostic protocols for identifying dysregulated ALK in NSCLC.
- To discuss ALK inhibitors and resistance mechanisms in NSCLC treatment.
Main Methods:
- Literature review of ALK signaling pathways.
- Comparative analysis of molecular diagnostic techniques for ALK.
- Review of clinical data on ALK inhibitors and resistance.
Main Results:
- ALK dysregulation is a significant oncogenic driver across multiple malignancies.
- Molecular testing is essential for identifying patients eligible for ALK-targeted therapy.
- Crizotinib and newer ALK inhibitors offer effective treatment options for ALK-positive NSCLC.
Conclusions:
- Targeted therapy for ALK-positive NSCLC significantly improves patient outcomes.
- Understanding ALK pathways and resistance mechanisms is critical for advancing cancer treatment.
- Diagnostic testing for ALK alterations is a cornerstone of personalized NSCLC therapy.
More Related Videos
10:35A Blood-based Test for the Detection of ROS1 and RET Fusion Transcripts from Circulating Ribonucleic Acid Using Digital Polymerase Chain Reaction
Published on: April 5, 2018
05:17Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025