Opinion statement
Personalized targeted therapy has emerged as a promising strategy in lung cancer treatment, with current attention focused on elucidation and detection of oncogenic drivers responsible for tumor initiation and maintenance and development of drug resistance. In lung cancer, several oncogenic drivers have been reported, triggering the application of tyrosine kinase inhibitors (TKIs) to target these dysfunctional genes. The anaplastic lymphoma kinase (ALK) rearrangement is responsible for about 4–7% of all non-small cell lung cancers (NSCLCs) and perhaps as high as a third in specific patient populations such as younger, male, non-smokers with advanced stage, epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) wild type, and signet ring cell adenocarcinoma with abundant intracytoplasmic mucin. The selection of patients based on their ALK status is vital on account of the high response rates with the ALK-targeted agents in this subset of patients. Standardization and validation of ALK rearrangement detection methods is essential for accurate and reproducible results. There are currently three detection methods widely available in clinical practice, including fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and polymerase chain reaction (PCR)-based next generation sequencing (NGS) technology. However, the choice of diagnostic methodology for ALK rearrangement detection in clinical practice remains a matter of debate. With accumulating data enumerating the advantages and disadvantages of each of the three methods, combining more than one testing method for ALK fusion detection may be beneficial for patients. In this review, we will discuss the current methods used in ALK rearrangement detection with emphasis on their key advantages and disadvantages.
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•• IASLC ATLAS OF ALK TESTING IN LUNG CANCER, final edition, First IASLC Press Printing October 2013. Available at: https://www.iaslc.org/publications/iaslc-atlas-alk-testing-lung-cancer. This guide is designed to help pathologists, laboratory scientists, and practicing physicians better understand the background, protocol, and interpretation of results of ALK testing in patients with advanced NSCLC.
•• IASLC ATLAS OF ALK AND ROS1 TESTING IN LUNG CANCER, second edition, First IASLC Press Printing December 2016. Available at: https://www.iaslc.org/publications/iaslc-atlas-alk-and-ros1-testing-lung-cancer. This publication is designed to help pathologists, scientists and physicians better understand the background, protocol and interpretation of results of ALK and ROS1 testing for NSCLC patients.
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Xiaomin Niu, Jody C. Chuang, and Gerald J. Berry declare that they have no conflict of interest. Heather A. Wakelee has received research funding through grants from Novartis, Pfizer, Bristol-Myers Squibb, XCovery, Celgene, Roche/Genentech, AstraZeneca/MedImmune, Lilly, Gilead, and Pharmacyclics; has served as an unpaid consultant for Roche/Genentech; and has received compensation from Peregrine, ACEA, and Pfizer for service as a consultant.
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Niu, X., Chuang, J.C., Berry, G.J. et al. Anaplastic Lymphoma Kinase Testing: IHC vs. FISH vs. NGS. Curr. Treat. Options in Oncol. 18, 71 (2017). https://doi.org/10.1007/s11864-017-0513-x
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DOI: https://doi.org/10.1007/s11864-017-0513-x