The anaplastic lymphoma kinase as an oncogene in solid tumors
Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
Center for Experimental Research and Medical Studies (CERMS), Citta della Salute e della Scienza, Torino, Italy
Department of Pathology, Children’s Hospital and Harvard Medical School, Boston, USA
European Research Initiative on ALK-related malignancies (ERIA)
01 June 2015
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.
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.