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ALK in Non-small Cell Lung Cancer


Globally, lung cancer is one of the most commonly reported cancers, with approximately 2.2 million new cases worldwide each year.1 Approximately 80% of lung cancers are non-small cell lung cancer (NSCLC).1 The prognosis for patients with lung cancer is poor; the 5-year survival rate for patients with NSCLC is approximately 17%.2 Existing therapies have limited therapeutic benefit in unselected NSCLC.3-5 Therefore, there is a need for new treatments which can improve outcomes for patients with advanced NSCLC.

There are three main histological NSCLC subtypes:

Squamous Cell Carcinoma
NSCLC not otherwise specified

Alternatively, NSCLC can be divided into molecular subsets based on specific biomarkers or mutations. Data indicate that 56% of non-squamous cell lung tumours have a driver mutation which can be detected through molecular testing.6 Identifying the particular molecular drivers present in individual patients may allow a personalised treatment approach to be used. One of the known molecular drivers in NSCLC is an aberrant form of anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase encoded by the ALK gene.7 ALK gene rearrangements lead to expression of ALK fusion proteins which have been identified as oncogenic drivers in a subset of patients with NSCLC. 7 Inhibition of ALK has been shown to be an effective treatment approach for patients with ALK-positive NSCLC.8-10

Figure. Evolution of knowledge of NSCLC.11,12

Evolution of knowledge of NSCLC


Adapted from Pao W, Girard N. Lancet Oncol 2011;12:175–180 & Shaw AT, et al. N Engl J Med 2011;365:158–167. Reproduced with permission from Elsevier and Massachusetts Medical Society ©2011.



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  7. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small cell lung cancer. Nature 2007;448:561–567
  8. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013;368:2385–2394
  9. Shaw AT, Kim DW, Mehra R, et al. Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 2014;370:1189–1197
  10. Gadgeel SM, Gandhi L, Riely GJ, et al. Safety and activity of alectinib against systemic disease and brain metastases in patients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer (AF-002JG): results from the dose-finding portion of a phase 1/2 study. Lancet Oncol 2014;15:1119–1128
  11. Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol 2011;12:175–180
  12. Shaw AT, Forcione DG, Digumarthy SR, Iafrate AJ. Case 21-2011: A 31-year-old man with ALK-positive adenocarcinoma of the lung. N Engl J Med 2011;365:158–167