Immunoassays for the quantification of ALK and phosphorylated ALK support the evaluation of on-target ALK inhibitors in neuroblastoma.
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Authors
Tucker, ER
Tall, JR
Danielson, LS
Gowan, S
Jamin, Y
Robinson, SP
Banerji, U
Chesler, L
Tall, JR
Danielson, LS
Gowan, S
Jamin, Y
Robinson, SP
Banerji, U
Chesler, L
Document Type
Journal Article
Date
2017-08-01
Date Accepted
2017-04-11
Abstract
Targeted inhibition of anaplastic lymphoma kinase (ALK) is a successful approach for the treatment of many ALK-aberrant malignancies; however, the presence of resistant mutations necessitates both the development of more potent compounds and pharmacodynamic methods with which to determine their efficacy. We describe immunoassays designed to quantitate phosphorylation of ALK, and their use in preclinical models of neuroblastoma, a pediatric malignancy in which gain-of-function ALK mutations predict a poor overall outcome to conventional treatment. Validation of the immunoassays is presented using a panel of neuroblastoma cell lines and evidence of on-target ALK inhibition provided by treatment of a genetically engineered murine model of neuroblastoma with two clinical ALK inhibitors, crizotinib and ceritinib, highlighting the superior efficacy of ceritinib.
Citation
Molecular oncology, 2017, 11 (8), pp. 996 - 1006
Source Title
Publisher
WILEY
ISSN
1574-7891
eISSN
1878-0261
Research Team
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Paediatric Solid Tumour Biology and Therapeutics
Pre-Clinical MRI
Medicine Drug Development Unit (de Bono)
Paediatric Solid Tumour Biology and Therapeutics
Pre-Clinical MRI