Crizotinib Synergizes with Chemotherapy in Preclinical Models of Neuroblastoma.

ABSTRACT:

Purpose

The presence of an ALK aberration correlates with inferior survival for patients with high-risk neuroblastoma. The emergence of ALK inhibitors such as crizotinib has provided novel treatment opportunities. However, certain ALK mutations result in de novo crizotinib resistance, and a phase I trial of crizotinib showed a lack of response in patients harboring those ALK mutations. Thus, understanding mechanisms of resistance and defining circumvention strategies for the clinic is critical.

Experimental design

The sensitivity of human neuroblastoma-derived cell lines, cell line-derived, and patient-derived xenograft (PDX) models with varying ALK statuses to crizotinib combined with topotecan and cyclophosphamide (topo/cyclo) was examined. Cultured cells and xenografts we

SUBMITTER: Krytska K 

PROVIDER: S-EPMC4755925 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature