%0 Journal Article
%T ALK in Neuroblastoma: Biological and Therapeutic Implications
%A Ricky M. Trigg
%A Suzanne D. Turner
%J Archive of "Cancers".
%D 2018
%R 10.3390/cancers10040113
%X 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¨C50%. 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
%K neuroblastoma
%K ALK
%K kinase inhibitors
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923368/