Novel pharmacodynamic biomarkers for MYCN protein and PI3K/AKT/mTOR pathway signaling in children with neuroblastoma.

ABSTRACT: There is an urgent need for improved therapies for children with high-risk neuroblastoma where survival rates remain low. MYCN amplification is the most common genomic change associated with aggressive neuroblastoma and drugs targeting PI3K/AKT/mTOR, to activate MYCN oncoprotein degradation, are entering clinical evaluation. Our aim was to develop and validate pharmacodynamic (PD) biomarkers to evaluate both proof of mechanism and proof of concept for drugs that block PI3K/AKT/mTOR pathway activity in children with neuroblastoma. We have addressed the issue of limited access to tumor biopsies for quantitative detection of protein biomarkers by optimizing a three-color fluorescence activated cell sorting (FACS) method to purify CD45-/GD2+/CD56+ neuroblastoma cells from bone marrow. We then

SUBMITTER: Smith JR 

PROVIDER: S-EPMC5423144 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature