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What is ALK?

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Last updated: May 2025

ALK for healthcare professionals

What is ALK-positive lung cancer?

ALK-positive (or ALK+) lung cancer is a type of non-small cell lung cancer (NSCLC). It occurs when the anaplastic lymphoma kinase (ALK) gene fuses with another gene (most commonly, a gene called EML4). The cause for this fusion is not known.

This abnormal gene fusion is commonly known as a type of oncogenic driver in NSCLC. It triggers and drives an abnormal signal within the cells to multiply uncontrollably. The new cells are replicas and therefore carry the same gene abnormality.

What are the clinical characteristics of ALK+ lung cancer?

ALK+ lung cancer only accounts for about 5% of advanced non-small cell lung cancers (Chevallier et al., 2021). ALK fusions occur predominantly in adenocarcinoma.

Up to 35% of patients with ALK+ lung cancer will have brain metastases at presentation (Gillespie, C.S. et al.2023).

ALK+ lung cancer can occur in anyone, but below are a few factors that tend to be seen more commonly:

  • ALK+ lung cancer is more common in those who are younger than the average lung cancer patient. The median age of patients with ALK-rearranged NSCLC is given as 50-52 (LoPiccolo et al., 2024), while the average age of lung cancer patients generally is 74 (National Lung Cancer Audit State of the Nation, 2024)
  • Other mutation-driven non-small cell lung cancers, such as those with an EGFR mutation, tend to be more common in female patients than in male patients (Lindeman et al., 2013), but these differences are generally not found in ALK+ lung cancer cases
  • ALK+ lung cancer is more common in light smokers or 'never-smokers' (Williams et al., 2016). Never-smokers are commonly defined as people who have smoked fewer than 100 cigarettes in their lifetime (Klemperer et al., 2021)

While tobacco-related lung cancer is the most common cause of cancer deaths globally, deaths from lung cancer in never smokers (LCINS) also rank highly. LCINS was the fifth highest cause of cancer deaths globally in 2020 (LoPiccolo et al., 2024).

References

Please be aware that the following links are current (as of April 2025), some may reside behind a paywall.

  • Chevallier, M. et al. (2021) ‘Oncogenic driver mutations in non-small cell lung cancer: Past, present and future.’, World journal of clinical oncology, 12(4), pp. 217–237. Available at: doi.org
  • Li, T., Kung, H.-J., Mack, P. C., & Gandara, D. R. (2013). Genotyping and Genomic Profiling of Non–Small-Cell Lung Cancer: Implications for Current and Future Therapies. Journal of Clinical Oncology, 31(8), 1039–1049. Available at: doi.org
  • Khan, S. et al. (2023) Lung cancer in never smokers (LCINS): development of a UK national research strategy. BJC Reports, 1(21). Available at: doi.org
  • ESMO OncologyPRO, ‘ALK in Lung Cancer: ESMO Biomarker Factsheet’, ALK in Lung Cancer: ESMO Biomarker Factsheet. Accessed 28 April 2025. Available at: ALK in Lung Cancer: ESMO Biomarker Factsheet
  • Gillespie, C.S. et al. (2023) ‘Genomic Alterations and the Incidence of Brain Metastases in Advanced and Metastatic NSCLC: A Systematic Review and Meta-Analysis’, Journal of Thoracic Oncology. Elsevier Inc., pp. 1703–1713. Available at: doi.org
  • Klemperer, E.M. et al. (2021) ‘Tobacco and Nicotine Use Among US Adult “Never Smokers” in Wave 4 (2016–2018) of the Population Assessment of Tobacco and Health Study’, Nicotine & Tobacco Research, 23(7), pp. 1199–1207. Available at: doi.org
  • Lindeman, N.I. et al. (2013) ‘Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors: Guideline from the College of American Pathologists, International Association for the Study of Lung Cancer, and Association for Molecular Pathology’,
    Journal of Thoracic Oncology, 8(7), pp. 823–859. Available at: doi.org
  • LoPiccolo, J. et al. (2024) ‘Lung cancer in patients who have never smoked — an emerging disease’, Nature Reviews Clinical Oncology. Springer Nature, pp. 121–146. Available at: doi.org
  • National Lung Cancer Audit. (2024) National Lung Cancer Audit State of the Nation 2024. Available at: lungcanceraudit.org.uk
    (Accessed: 28 April 2025)
  • Williams, A.S. et al. (2016) ‘ALK+ lung adenocarcinoma in never smokers and long-term ex-smokers: prevalence and detection by immunohistochemistry and fluorescence in situ hybridization’, Virchows Archiv, 469(5), pp. 533–540. Available at: doi.org
  • Zhang, S. S., Nagasaka, M., Zhu, V. W., & Ou, S.-H. I. (2021). Going beneath the tip of the iceberg. Identifying and understanding EML4-ALK variants and TP53 mutations to optimize treatment of ALK fusion positive (ALK+) NSCLC. Lung Cancer, 158, 126–136. Available at: doi.org
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