Tackling Crizotinib Resistance: The Pathway from Drug Discovery to the Pediatric Clinic.

ABSTRACT: Neuroblastoma is a childhood malignancy that has not yet benefitted from the rapid progress in the development of small-molecule therapeutics for cancer. An opportunity to take advantage of pharmaceutical innovation in this area arose when the identification of ALK fusion proteins in non-small cell lung cancer (NSCLC) occurred in parallel to the discovery of point mutations of ALK in neuroblastomas. ALK is now known to be a marker of poor outcome in neuroblastoma, and therefore, urgent development of specific ALK inhibitors to treat this devastating disease is a necessity. However, the translation of small molecules from adult directly into pediatric practice has thus far been challenging, due to mutation-specific structural variances in the ALK kinase domain. We discuss how the most recen

SUBMITTER: Tucker ER 

PROVIDER: S-EPMC4539575 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature