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ALK in Neuroblastoma: Biological and Therapeutic Implications

Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge CB2 0QQ, UK
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Cancers 2018, 10(4), 113; https://doi.org/10.3390/cancers10040113
Received: 21 March 2018 / Revised: 5 April 2018 / Accepted: 6 April 2018 / Published: 10 April 2018
Neuroblastoma (NB) is the most common and deadly solid tumour in children. Despite the development of new treatment options for high-risk NB, over half of patients relapse and five-year survival remains at 40–50%. Therefore, novel treatment strategies aimed at providing long-term disease remission are urgently sought. ALK, encoding the anaplastic lymphoma kinase receptor, is altered by gain-of-function point mutations in around 14% of high-risk NB and represents an ideal therapeutic target given its low or absent expression in healthy tissue postnatally. Small-molecule inhibitors of Anaplastic Lymphoma Kinase (ALK) approved in ALK fusion-positive lung cancer are currently undergoing clinical assessment in patients with ALK-mutant NB. Parallel pre-clinical studies are demonstrating the efficacy of ALK inhibitors against common ALK variants in NB; however, a complex picture of therapeutic resistance is emerging. It is anticipated that long-term use of these compounds will require combinatorial targeting of pathways downstream of ALK, functionally-related ‘bypass’ mechanisms and concomitant oncogenic pathways. View Full-Text
Keywords: neuroblastoma; ALK; kinase inhibitors neuroblastoma; ALK; kinase inhibitors
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Trigg, R.M.; Turner, S.D. ALK in Neuroblastoma: Biological and Therapeutic Implications. Cancers 2018, 10, 113.

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