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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.

Author information

1
Department of Clinical Chemistry.
2
Department of Pulmonology, VU University Medical Center.
3
Department of Thoracic Oncology, Netherlands Cancer Institute.
4
Department of Medical Oncology, VU University Medical Center, Amsterdam, the Netherlands.
5
Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy.

Abstract

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.

KEYWORDS:

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

Conflict of interest statement

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

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