{"entity":{"id":"alk-fusion","kind":"biomarker","name":"ALK fusion (ALK-positive)","aka":["ALK fusion","ALK rearrangement","ALK-positive","ALK+","EML4-ALK","EML4::ALK","ALK translocation","ALK gene rearrangement"],"tldr":"An ALK fusion, usually EML4::ALK, is a swapped piece of chromosome 2 that turns the ALK kinase on permanently in about 4 percent of lung adenocarcinomas. Seven ALK inhibitors are approved for it, including alectinib after surgery.","summary":"ALK rearrangements are detected by break-apart FISH (Vysis), immunohistochemistry (Ventana D5F3), or DNA and RNA sequencing; the FDA list carries all three routes as companion diagnostics. Crizotinib, ceritinib, alectinib, brigatinib, lorlatinib and ensartinib are labelled for ALK-positive metastatic NSCLC 'as detected by an FDA-approved test', and alectinib for adjuvant treatment after resection of tumours 4 cm or larger or node-positive (ALINA). Crizotinib is also labelled for ALK-positive anaplastic large cell lymphoma and inflammatory myofibroblastic tumour. Alectinib's label allows selection on tumour tissue or plasma.","asOf":"2026-09-23","links":[{"label":"ALECENSA prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=42c49deb-713b-427a-9670-08af08adcffb"},{"label":"Lorbrena prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=004f93d7-a1cd-4b67-9207-31cdcb5c5976"}],"tags":["biomarker","fusion"],"related":["ros1-fusion","ret-fusion","ntrk-fusion"],"cancers":["nsclc","pancreatic","kras-wild-type-pdac"],"sections":[],"technologies":[],"targets":[],"drugs":["alectinib","lorlatinib","crizotinib","brigatinib","ceritinib","ensartinib","foundationone-cdx"],"companies":[],"institutions":[],"pathways":[],"terms":["gene-fusion","fish","tki-term"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-singhi-alk-rearrangements-pancreatic-jnccn-2017","paper-philip-kras-wild-type-pancreatic-ccr-2022","paper-soda-eml4-alk-fusion-nature-2007","paper-kris-lung-cancer-mutation-consortium-jama-2014","paper-gainor-alk-resistance-mutations-cancer-discov-2016","paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019","paper-lindeman-lung-molecular-testing-guideline-jto-2018"],"journals":[],"dependsOn":[],"notes":["Pancreatic ductal adenocarcinoma: ALK fusions in 0.16% of 3,170 tumours, all KRAS wild-type and all in patients under 50 (1.3% of that age group), with benefit from ALK inhibitors in 3 of 4 treated (Singhi 2017).","Lung cancer: 3 to 6% of adenocarcinomas by panel and 8% by fluorescence in situ hybridisation in the Lung Cancer Mutation Consortium, with EML4 the partner in the large majority (Soda 2007, Kris 2014; cBioPortal). Immunohistochemistry is an acceptable screen and a DNA panel that does not bait the breakpoint introns will read wild-type (Lindeman 2018). At progression the gene is read again for resistance mutations, which decide whether a third-generation inhibitor is the right next step (Gainor 2016, Shaw 2019)."],"target":"alk","measurement":"sequencing-variant","scoringRule":{"text":"An ALK gene rearrangement or fusion by break-apart FISH (15 percent or more of cells with split or isolated 3' signals on the Vysis kit), ALK protein expression by the Ventana D5F3 IHC assay, or a fusion transcript or rearrangement by sequencing of tissue or plasma.","quote":"ALK rearrangements","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","sourceLabel":"FDA: List of FDA-Authorized Companion Diagnostic Devices"},"thresholds":[{"value":"ALK-positive (adjuvant, tumours >= 4 cm or node positive)","drugId":"alectinib","cancerId":"nsclc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=42c49deb-713b-427a-9670-08af08adcffb","quote":"adjuvant treatment in adult patients following tumor resection of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) (tumors ≥ 4 cm or node positive) as detected by an FDA-approved test.","status":"current"},{"value":"ALK-positive","drugId":"lorlatinib","cancerId":"nsclc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=004f93d7-a1cd-4b67-9207-31cdcb5c5976","quote":"LORBRENA ® is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.","status":"current"},{"value":"ALK-positive or ROS1-positive","drugId":"crizotinib","cancerId":"nsclc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2a51b0de-47d6-455e-a94c-d2c737b04ff7","quote":"adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test.","status":"current"},{"value":"ALK-positive","drugId":"brigatinib","cancerId":"nsclc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0fe9ff20-d402-41f3-bc1e-7002ea7007db","quote":"ALUNBRIG is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test","status":"current"},{"value":"ALK-positive, ALK inhibitor-naive","drugId":"ensartinib","cancerId":"nsclc","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e1b2f79-678a-472a-b924-66909c8a4b2e","quote":"ENSACOVE is indicated for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC)as detected by an FDA-approved test","status":"current"}],"tests":["foundationone-cdx","foundationone-liquid-cdx","guardant360-cdx","tempus-xt","trusight-oncology-comprehensive","caris-mi-cancer-seek"],"assays":["alk-vysis-fish","alk-d5f3","foundationone-cdx-panel"],"companionDiagnostics":[{"device":"Vysis ALK Break Apart FISH Probe Kit","maker":"Abbott Molecular","companyId":"abbott","drugs":["crizotinib"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Tissue","pma":"P110012 (08/26/2011)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Vysis ALK Break Apart FISH Probe Kit","maker":"Abbott Molecular","companyId":"abbott","drugs":["ensartinib"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Tissue","pma":"P110012/S022 (08/05/2025)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Ventana ALK (D5F3) CDx Assay","maker":"Ventana Medical Systems (Roche)","drugs":["alectinib"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Tissue","pma":"P140025/S006 (11/06/2017)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Ventana ALK (D5F3) CDx Assay","maker":"Ventana Medical Systems (Roche)","drugs":["lorlatinib"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Tissue","pma":"P140025/S014 (03/03/2021)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"FoundationOne CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["alectinib","crizotinib","ceritinib"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Tissue","pma":"P170019 (11/30/2017)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"FoundationOne Liquid CDx","maker":"Foundation Medicine","companyId":"foundation-medicine","drugs":["alectinib"],"indication":"Non-Small Cell Lung Cancer (NSCLC) - Plasma","pma":"P200006 (10/26/2020)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"ALK-positive lung cancer is treated first with an ALK tablet, usually alectinib or lorlatinib, instead of chemotherapy or immunotherapy, and responses often last years. After surgery, two years of alectinib is on label for larger or node-positive tumours. If one ALK tablet stops working, others are approved after it."},"route":"/biomarkers/alk-fusion/","neighbours":{"biomarker":[{"id":"alk-resistance-mutation","kind":"biomarker","name":"ALK kinase-domain resistance mutation (G1202R and the rest)","route":"/biomarkers/alk-resistance-mutation/"},{"id":"ntrk-fusion","kind":"biomarker","name":"NTRK1/2/3 gene fusion","route":"/biomarkers/ntrk-fusion/"},{"id":"ret-fusion","kind":"biomarker","name":"RET fusion and RET mutation","route":"/biomarkers/ret-fusion/"},{"id":"ros1-fusion","kind":"biomarker","name":"ROS1 fusion (ROS1-positive)","route":"/biomarkers/ros1-fusion/"}],"cancer":[{"id":"kras-wild-type-pdac","kind":"cancer","name":"KRAS wild-type pancreatic ductal adenocarcinoma","route":"/cancers/kras-wild-type-pdac/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"drug":[{"id":"alectinib","kind":"drug","name":"Alectinib","route":"/drugs/alectinib/"},{"id":"brigatinib","kind":"drug","name":"Brigatinib","route":"/drugs/brigatinib/"},{"id":"ceritinib","kind":"drug","name":"Ceritinib","route":"/drugs/ceritinib/"},{"id":"crizotinib","kind":"drug","name":"Crizotinib","route":"/drugs/crizotinib/"},{"id":"ensartinib","kind":"drug","name":"Ensartinib","route":"/drugs/ensartinib/"},{"id":"foundationone-cdx","kind":"drug","name":"FoundationOne CDx / Liquid CDx","route":"/drugs/foundationone-cdx/"},{"id":"lorlatinib","kind":"drug","name":"Lorlatinib","route":"/drugs/lorlatinib/"}],"term":[{"id":"fish","kind":"term","name":"FISH / ISH (in situ hybridisation)","route":"/terms/fish/"},{"id":"gene-fusion","kind":"term","name":"Gene fusion","route":"/terms/gene-fusion/"},{"id":"tki-term","kind":"term","name":"Tyrosine kinase inhibitor (TKI)","route":"/terms/tki-term/"}],"paper":[{"id":"paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019","kind":"paper","name":"ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer","route":"/key-papers/paper-shaw-alk-resistance-mutations-lorlatinib-jco-2019/"},{"id":"paper-singhi-alk-rearrangements-pancreatic-jnccn-2017","kind":"paper","name":"Identification of targetable ALK rearrangements in pancreatic ductal adenocarcinoma","route":"/key-papers/paper-singhi-alk-rearrangements-pancreatic-jnccn-2017/"},{"id":"paper-soda-eml4-alk-fusion-nature-2007","kind":"paper","name":"Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer","route":"/key-papers/paper-soda-eml4-alk-fusion-nature-2007/"},{"id":"paper-philip-kras-wild-type-pancreatic-ccr-2022","kind":"paper","name":"Molecular characterization of KRAS wild-type tumors in patients with pancreatic adenocarcinoma","route":"/key-papers/paper-philip-kras-wild-type-pancreatic-ccr-2022/"},{"id":"paper-gainor-alk-resistance-mutations-cancer-discov-2016","kind":"paper","name":"Molecular mechanisms of resistance to first- and second-generation ALK inhibitors in ALK-rearranged lung cancer","route":"/key-papers/paper-gainor-alk-resistance-mutations-cancer-discov-2016/"},{"id":"paper-shaw-alk-l1198f-resensitisation-nejm-2016","kind":"paper","name":"Resensitization to crizotinib by the lorlatinib ALK resistance mutation L1198F","route":"/key-papers/paper-shaw-alk-l1198f-resensitisation-nejm-2016/"},{"id":"paper-lindeman-lung-molecular-testing-guideline-jto-2018","kind":"paper","name":"Updated molecular testing guideline for the selection of lung cancer patients for treatment with targeted tyrosine kinase inhibitors","route":"/key-papers/paper-lindeman-lung-molecular-testing-guideline-jto-2018/"},{"id":"paper-kris-lung-cancer-mutation-consortium-jama-2014","kind":"paper","name":"Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs","route":"/key-papers/paper-kris-lung-cancer-mutation-consortium-jama-2014/"}],"target":[{"id":"alk","kind":"target","name":"ALK","route":"/targets/alk/"}]}}