• Srividya Srinivasamaharaj, Bilal Khameze Salame, Jorge Rios-Perez, Goetz Kloecker, and Cesar A Perez.
• a Division of Medical Oncology and Hematology, James Graham Brown Cancer Center , University of Louisville , Louisville , KY , USA.
• Expert Rev Anticancer Ther. 2016 Dec 1; 16 (12): 1227-1233.

IntroductionThe identification of anaplastic lymphoma kinase (ALK) gene rearrangements in subsets of non-small cell lung cancer patients has provided with unparalleled opportunities to hinder the progression of this disease through targeting the activity of these specific molecules. Unfortunately most patients develop disease progression in less than a year of treatment with crizotinib, the first-generation ALK-inhibitor. Areas covered: We review the resistance mechanisms to ALK inhibitors as well as an overview of the clinical activity of the alectinib, a second generation ALK inhibitor. Expert commentary: Second generation ALK inhibitors as alectinib and ceritinib can overcome crizotinib-resistant mutations and improve central nervous system control. Novel third-generation inhibitors and combination of agents give hope of achieving an even longer disease control in the next decade.

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