2. Academic Validation
  3. Immunoassays for the quantification of ALK and phosphorylated ALK support the evaluation of on-target ALK inhibitors in neuroblastoma

Immunoassays for the quantification of ALK and phosphorylated ALK support the evaluation of on-target ALK inhibitors in neuroblastoma

  • Mol Oncol. 2017 Aug;11(8):996-1006. doi: 10.1002/1878-0261.12069.
Elizabeth R Tucker 1,  Jennifer R Tall 1 2,  Laura S Danielson 1,  Sharon Gowan 3,  Yann Jamin 4,  Simon P Robinson 4,  Udai Banerji 2,  Louis Chesler 1
Affiliations

Affiliations

  • 1 Paediatric Solid Tumour Biology and Therapeutics Team, Division of Clinical Studies and Cancer Therapeutics Division, The Institute of Cancer Research, Sutton, Surrey, UK.
  • 2 Clinical Pharmacodynamic Biomarker Team, Cancer Therapeutics Division, The Institute of Cancer Research, Sutton, Surrey, UK.
  • 3 Tumour Biology and Metastasis, Cancer Therapeutics Division, The Institute of Cancer Research, Sutton, Surrey, UK.
  • 4 Division of Radiotherapy and Imaging, The Institute of Cancer Research, Sutton, Surrey, UK.
PMID: 28432815 DOI: 10.1002/1878-0261.12069
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.

Keywords

ALK; neuroblastoma.

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