PMID- 37577307 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230815 IS - 2218-6751 (Print) IS - 2226-4477 (Electronic) IS - 2218-6751 (Linking) VI - 12 IP - 7 DP - 2023 Jul 31 TI - A narrative review of methods for the identification of ALK fusions in patients with non-small cell lung carcinoma. PG - 1549-1562 LID - 10.21037/tlcr-22-855 [doi] AB - BACKGROUND AND OBJECTIVE: This narrative review is intended to provide pragmatic knowledge of current methods for the search of anaplastic lymphoma kinase (ALK) fusions in patients with non-small cell lung carcinoma (NSCLC). This information is very timely, because a recent survey has identified that almost 50% of patients with advanced NSCLC were not candidates for targeted therapies because of biomarker testing issues. METHODS: PubMed was searched from January 1(st), 2012 to February 28(th), 2023 using the following keywords: "ALK" and "lung", including reviews and our own work. KEY CONTENT AND FINDINGS: Testing rates have not reached 85% among patients' candidates to ALK inhibition. The advantages and disadvantages of the different analytical options [immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), real-time polymerase chain reaction and next-generation sequencing (NGS)] are discussed. The key factor for success in ALK testing is a deep understanding of the concept of "molecular redundancy". This notion has been recommended and endorsed by all the major professional organizations in the field and can be summarized as follows: "laboratories should ensure that test results that are unexpected, discordant, equivocal, or otherwise of low confidence are confirmed or resolved using an alternative method or sample". In-depth knowledge of the different ALK testing methodologies can help clinical and molecular tumor boards implement and maintain sensible algorithms for a rapid and effective detection of predictive biomarkers in patients with NSCLC. CONCLUSIONS: Multimodality testing has the potential to increase both the testing rate and the accuracy of ALK fusion identification. CI - 2023 Translational Lung Cancer Research. All rights reserved. FAU - Hernandez, Susana AU - Hernandez S AD - Pathology Department, Hospital Universitario 12 de Octubre, Research Institute Hospital 12 de Octubre (i+12), Madrid, Spain. FAU - Conde, Esther AU - Conde E AD - Pathology Department, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Research Institute Hospital 12 de Octubre (i+12), Ciberonc, Madrid, Spain. FAU - Alonso, Marta AU - Alonso M AD - Pathology Department, Hospital Universitario 12 de Octubre, Research Institute Hospital 12 de Octubre (i+12), Madrid, Spain. FAU - Illarramendi, Adrian AU - Illarramendi A AD - Pathology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. FAU - Bote de Cabo, Helena AU - Bote de Cabo H AD - Oncology Department, Hospital Universitario 12 de Octubre, H12O-CNIO Lung Cancer Clinical Research Unit, Research Institute Hospital 12 de Octubre (i+12)/Spanish National Cancer Research Center (CNIO), Madrid, Spain. FAU - Zugazagoitia, Jon AU - Zugazagoitia J AD - Oncology Department, Hospital Universitario 12 de Octubre, H12O-CNIO Lung Cancer Clinical Research Unit, Research Institute Hospital 12 de Octubre (i+12)/Spanish National Cancer Research Center (CNIO), Ciberonc, Madrid, Spain. FAU - Paz-Ares, Luis AU - Paz-Ares L AD - Oncology Department, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, H12O-CNIO Lung Cancer Clinical Research Unit, Research Institute Hospital 12 de Octubre (i+12)/Spanish National Cancer Research Center (CNIO), Ciberonc, Madrid, Spain. FAU - Lopez-Rios, Fernando AU - Lopez-Rios F AD - Pathology Department, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Research Institute Hospital 12 de Octubre (i+12), Ciberonc, Madrid, Spain. LA - eng PT - Journal Article PT - Review DEP - 20230711 PL - China TA - Transl Lung Cancer Res JT - Translational lung cancer research JID - 101646875 PMC - PMC10413037 OTO - NOTNLM OT - Anaplastic lymphoma kinase (ALK) OT - fluorescence in situ hybridization (FISH) OT - immunohistochemistry (IHC) OT - next-generation sequencing (NGS) OT - non-small cell lung carcinoma (NSCLC) COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-855/coif). The series "ALK Positive NSCLC" was commissioned by the editorial office without any funding or sponsorship. SH receives honoraria from Roche, Pfizer and Thermo Fisher Scientific and research funding from Roche and Thermo Fisher Scientific. EC receives honoraria from Roche, Thermo Fisher Scientific, Pfizer and Takeda and research funding from Roche and Thermo Fisher Scientific. JZ has served as a consultant for Astra Zeneca, BMS, Roche and Novartis, and received honoraria and travels honoraria from BMS, Roche, Astra Zeneca and Nanostring and research funding from BMS, Astra Zeneca and Roche. LPA has served as a consultant for Lilly, MSD, Roche, Pharmamar, Merck, Astra Zeneca, Novartis, Servier, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda and Daichii, and received honoraria from Astra Zeneca, Janssen, Merck and Mirati and research funding from MSD, AstraZeneca, Pfizer and BMS. FLR receives honoraria from Roche, Thermo Fisher Scientific, Pfizer and Takeda, and research funding from Roche and Thermo Fisher. The authors have no other conflicts of interest to declare. EDAT- 2023/08/14 06:42 MHDA- 2023/08/14 06:43 PMCR- 2023/07/31 CRDT- 2023/08/14 04:57 PHST- 2023/03/01 00:00 [received] PHST- 2023/06/25 00:00 [accepted] PHST- 2023/08/14 06:43 [medline] PHST- 2023/08/14 06:42 [pubmed] PHST- 2023/08/14 04:57 [entrez] PHST- 2023/07/31 00:00 [pmc-release] AID - tlcr-12-07-1549 [pii] AID - 10.21037/tlcr-22-855 [doi] PST - ppublish SO - Transl Lung Cancer Res. 2023 Jul 31;12(7):1549-1562. doi: 10.21037/tlcr-22-855. Epub 2023 Jul 11.