New strategies in neuroblastoma: Therapeutic targeting of MYCN and ALK.

Barone, Giuseppe, Anderson, John, Pearson, Andrew D J, Petrie, Kevin and Chesler, Louis (2013) New strategies in neuroblastoma: Therapeutic targeting of MYCN and ALK. Clinical cancer research : an official journal of the American Association for Cancer Research, 19 (21). pp. 5814-21. ISSN 1078-0432

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Abstract

Clinical outcome remains poor in patients with high-risk neuroblastoma, in which chemoresistant relapse is common following high-intensity conventional multimodal therapy. Novel treatment approaches are required. Although recent genomic profiling initiatives have not revealed a high frequency of mutations in any significant number of therapeutically targeted genes, two exceptions, amplification of the MYCN oncogene and somatically acquired tyrosine kinase domain point mutations in anaplastic lymphoma kinase (ALK), present exciting possibilities for targeted therapy. In contrast with the situation with ALK, in which a robust pipeline of pharmacologic agents is available from early clinical use in adult malignancy, therapeutic targeting of MYCN (and MYC oncoproteins in general) represents a significant medicinal chemistry challenge that has remained unsolved for two decades. We review the latest approaches envisioned for blockade of ALK activity in neuroblastoma, present a classification of potential approaches for therapeutic targeting of MYCN, and discuss how recent developments in targeting of MYC proteins seem to make therapeutic inhibition of MYCN a reality in the clinic.

Item Type: Article
Subjects: Sciences > Biomedical Sciences
Sciences > Health Sciences
Divisions: Faculty of Health Sciences and Wellbeing > School of Medicine
Depositing User: Kevin Petrie
Date Deposited: 18 Aug 2020 18:08
Last Modified: 19 Aug 2020 09:40
URI: http://sure.sunderland.ac.uk/id/eprint/12436
ORCID for Kevin Petrie: ORCID iD orcid.org/0000-0002-9805-9152

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