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Review
The anaplastic lymphoma kinase as an oncogene in solid tumors
Claudia Voena1,2,3,Silvia Peola1,2,Roberto Chiarle1,2,3,4,*
1
Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
2
Center for Experimental Research and Medical Studies (CERMS), Citta della Salute e della Scienza, Torino, Italy
3
Department of Pathology, Children’s Hospital and Harvard Medical School, Boston, USA
4
European Research Initiative on ALK-related malignancies (ERIA)
DOI: 10.2741/S440 Volume 7 Issue 2, pp.269-282
Published: 01 June 2015
(This article belongs to the Special Issue ALK: 20 years of discoveries)
*Corresponding Author(s):  
Roberto Chiarle
E-mail:  
roberto.chiarle@childrens.harvard.edu
Abstract

Twenty years ago anaplastic lymphoma kinase (ALK) was discovered in anaplastic large cell lymphoma (ALCL), but the interest in ALK as an oncogene grew only in recent years when ALK rearrangements were reported as recurrent genetic lesions in lung carcinoma and activating single point mutations were described in neuroblastoma. In this review we will describe the main features of ALK-rearranged solid tumors, with particular emphasis to NSCLC and neuroblastoma. We will discuss the numerous in vitro and in vivo studies that confirmed ALK as the “driver” oncogene in these tumors and the achievements in clinical settings with ALK inhibitors that validated ALK as a therapeutic target. We will finally end with the description of putative innovative therapeutic approaches that are on going to overcome acquired resistance that invariably occurs in crizotinib treated NSCLC patients or intrinsic resistance to crizotinb therapy reported in neuroblastoma.

Key words
ALK-rearrangements, Non-Small Cell Lung Cancer, ALK mutations, Neuroblastoma, Solid tumors, Targeted therapy, Review
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Claudia Voena, Silvia Peola, Roberto Chiarle. The anaplastic lymphoma kinase as an oncogene in solid tumors. Frontiers in Bioscience-Scholar. 2015. 7(2); 269-282.