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ALK in Neuroblastoma: Biological and Therapeutic Implications
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 a...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923368/ https://www.ncbi.nlm.nih.gov/pubmed/29642598 http://dx.doi.org/10.3390/cancers10040113 |
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author | Trigg, Ricky M. Turner, Suzanne D. |
author_facet | Trigg, Ricky M. Turner, Suzanne D. |
author_sort | Trigg, Ricky M. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5923368 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-59233682018-05-03 ALK in Neuroblastoma: Biological and Therapeutic Implications Trigg, Ricky M. Turner, Suzanne D. Cancers (Basel) Review 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. MDPI 2018-04-10 /pmc/articles/PMC5923368/ /pubmed/29642598 http://dx.doi.org/10.3390/cancers10040113 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Trigg, Ricky M. Turner, Suzanne D. ALK in Neuroblastoma: Biological and Therapeutic Implications |
title | ALK in Neuroblastoma: Biological and Therapeutic Implications |
title_full | ALK in Neuroblastoma: Biological and Therapeutic Implications |
title_fullStr | ALK in Neuroblastoma: Biological and Therapeutic Implications |
title_full_unstemmed | ALK in Neuroblastoma: Biological and Therapeutic Implications |
title_short | ALK in Neuroblastoma: Biological and Therapeutic Implications |
title_sort | alk in neuroblastoma: biological and therapeutic implications |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923368/ https://www.ncbi.nlm.nih.gov/pubmed/29642598 http://dx.doi.org/10.3390/cancers10040113 |
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