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Personalized treatment in advanced ALK-positive non-small cell lung cancer: from bench to clinical practice

Authors Passaro A, Lazzari C, Karachaliou N, Spitaleri G, Pochesci A, Catania C, Rosell R, de Marinis F

Received 7 June 2016

Accepted for publication 3 September 2016

Published 17 October 2016 Volume 2016:9 Pages 6361—6376


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 5

Editor who approved publication: Dr Samir Farghaly

Antonio Passaro,1 Chiara Lazzari,1,2 Niki Karachaliou,3 Gianluca Spitaleri,1 Alessia Pochesci,1 Chiara Catania,1 Rafael Rosell,4 Filippo de Marinis1

1Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy; 2Department of Medical Oncology, Division of Experimental Medicine, San Raffaele Scientific Institute, Milan, Italy; 3Oncology Institute Dr Rosell, Quiron-Dexeus University Hospital, Barcelona, Spain; 4Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain

Abstract: The discovery of anaplastic lymphoma kinase (ALK) gene rearrangements and the development of tyrosine kinase inhibitors (TKI) that target them have achieved unprecedented success in the management of patients with ALK-positive non-small cell lung cancer (NSCLC). Despite the high efficacy of crizotinib, the first oral ALK TKI approved for the treatment of ALK-positive NSCLC, almost all patients inevitably develop acquired resistance, showing disease progression in the brain or in other parenchymal sites. Second- or third-generation ALK TKIs have shown to be active in crizotinib-pretreated or crizotinib-naïve ALK-positive patients, even in those with brain metastases. In this review, the current knowledge regarding ALK-positive NSCLC, focusing on the biology of the disease and the available therapeutic options are discussed.

Keywords: ALK, NSCLC, crizotinib, ceritinib, alectinib, brigatinib, lorlatinib, brain metastases

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