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Review
. 2016 Oct 17:9:6361-6376.
doi: 10.2147/OTT.S98347. eCollection 2016.

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

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

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

Antonio Passaro et al. Onco Targets Ther. .

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; alectinib; brain metastases; brigatinib; ceritinib; crizotinib; lorlatinib.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
ALK signaling pathway. Abbreviations: ALK, anaplastic lymphoma kinase; EML4, echinoderm microtubule-associated protein like 4; FISH, fluorescence in situ hybridization; HELP, hydrophobic EMAP-like protein; IHC, immunohistochemistry; mTOR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3-kinase; RT-PCR, reverse transcription polymerase chain reaction; STAT3, signal transducer and activator of transcription 3; WD, tryptophan–aspartic acid.
Figure 2
Figure 2
Crizotinib structure.
Figure 3
Figure 3
Ceritinib structure.
Figure 4
Figure 4
Alectinib structure.
Figure 5
Figure 5
Brigatinib structure.
Figure 6
Figure 6
Lorlatinib structure.
See this image and copyright information in PMC

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