Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Trigg, Ricky M., Turner, Suzanne D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
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
_version_ 1783318325841887232
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
work_keys_str_mv AT triggrickym alkinneuroblastomabiologicalandtherapeuticimplications
AT turnersuzanned alkinneuroblastomabiologicalandtherapeuticimplications