ALK is a therapeutic target in NSCLC, with
gene fusions occurring in ~5%
of patients5-7
Patients with ALK+ NSCLC require an effective treatment with both systemic and central nervous system (CNS) activity3–6

The most common sites of metastasis for patients with all types of stage IV lung cancer8

CNS 30-40%8
(36% for ALK+ NSCLC)3Lung 18.5%8
Bone 16.4%8
Despite advances in therapy for ALK+ NSCLC, additional treatment options are needed to improve clinical outcomes3
High-quality testing such as IHC, FISH and NGS are needed to identify patients with actionable ALK gene fusions9

Testing for ALK+ rearrangement should be systematically carried out in advanced NSCLC10
- ALK testing involves the detection of ALK gene rearrangements or overexpression of ALK proteins.11
- FISH, IHC and RT-PCR are currently used in routine clinical practice.
- NGS offers more comprehensive detection of ALK fusions and other oncogenic driver alterations.
The ALK protein plays an important role in healthy tissue and if altered by fusion events or mutations drives cancer through aberrant signalling26
ALK gene fusions create oncogenic proteins
- The ALK gene can combine with multiple other gene partners to create an oncogenic fusion protein26
- So far, ~30 different fusions have been detected26

The oncogenic ALK protein drives cancer through aberrant signalling26
- The oncogenic fusion or mutated ALK protein constitutively activates signalling cascades implicated in cell proliferation, survival and angiogenesis26


Footnotes:
CNS, central nervous system; FISH, fluorescence in situ hybridisation; IHC, immunohistochemistry; NGS, next-generation sequencing; NSCLC, non-small cell lung cancer; RT-PCR, reverse transcription polymerase chain reaction.
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Oikawa A, et al. Oncol Lett 2012;3:629–634.
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Planchard D. Ann Oncol 2018;29:iv192–iv237.
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International Association for the Study of Lung Cancer. IASLC Atlas of ALK and ROS1 testing in lung cancer. Available at: https://www.iaslc.org/research-education/publications-resources-guidelines/iaslc-atlas-alk-and-ros1-testing-lung-cancer (Accessed November 2020).
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Du. et al. Thoracic Cancer 2018; 9(4): 423-430
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