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Cancers (Basel). 2018 Apr 10;10(4). pii: E113. doi: 10.3390/cancers10040113.

ALK in Neuroblastoma: Biological and Therapeutic Implications.

Author information

1
Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge CB2 0QQ, UK. rt473@cam.ac.uk.
2
Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge CB2 0QQ, UK. sdt36@cam.ac.uk.

Abstract

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.

KEYWORDS:

ALK; kinase inhibitors; neuroblastoma

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