ALK in Neuroblastoma: Biological and Therapeutic Implications.
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Trigg, R., & Turner, S. (2018). ALK in Neuroblastoma: Biological and Therapeutic Implications.. Cancers, 10 (4)https://doi.org/10.3390/cancers10040113
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.
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (675712)
Children with Cancer UK (16-209)
Embargo Lift Date
External DOI: https://doi.org/10.3390/cancers10040113
This record's URL: https://www.repository.cam.ac.uk/handle/1810/277711
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/