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Onco Targets Ther. 2017 Sep 13;10:4535-4541. doi: 10.2147/OTT.S109493. eCollection 2017.

Anaplastic lymphoma kinase inhibition in metastatic non-small cell lung cancer: clinical impact of alectinib.

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Department of Clinical Chemistry.
Department of Pulmonology, VU University Medical Center.
Department of Thoracic Oncology, Netherlands Cancer Institute.
Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy.


A subset of non-small cell lung cancer (NSCLC) tumors (5%) harbors an anaplastic lymphoma kinase (ALK) translocation that drives tumorigenesis. The clinically approved first-line treatment crizotinib specifically inhibits ALK and improves progression-free survival (PFS) in treated and untreated patients by 4 months compared to standard chemotherapy. While some patients relapse after crizotinib treatment due to resistance mutations in ALK, second-generation ALK inhibitors effectively induce tumor response and prolong PFS. Alectinib, a second-generation ALK inhibitor, has recently been approved for ALK-rearranged NSCLC after patients progressed on crizotinib. Alectinib is able to inhibit several crizotinib- and ceritinib-resistant ALK mutations in vitro. Furthermore, alectinib is a more potent tyrosine kinase inhibitor (TKI), with favorable safety profile, and has increased penetration into the central nervous system, inhibiting crizotinib-resistant brain metastases. The discovery of effective personalized therapies to combat ALK-rearranged NSCLC such as alectinib is an example of the importance of genomic profiling of NSCLC and provides an excellent template for future discoveries in managing these tumors.


acquired resistance; alectinib; anaplastic lymphoma kinase; crizotinib; non-small cell lung cancer; tyrosine kinase inhibitors

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Disclosure The authors report no conflicts of interest in this work.

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