Targeting MDM2 for Neuroblastoma Therapy: In Vitro and In Vivo Anticancer Activity and Mechanism of Action.

ABSTRACT:

Background

Neuroblastoma is an aggressive pediatric solid tumor with an overall survival rate of <50% for patients with high-risk disease. The majority (>98%) of pathologically-diagnosed neuroblastomas have wild-type p53 with intact functional activity. However, the mouse double minute 2 (MDM2) homolog, an E3 ubiquitin ligase, is overexpressed in neuroblastoma and leads to inhibition of p53. MDM2 also exerts p53-independent oncogenic functions. Thus, MDM2 seems to be an attractive target for the reactivation of p53 and attenuation of oncogenic activity in neuroblastoma.

Methods

In this study, we evaluated the anticancer activities and underlying mechanisms of action of SP141, a first-in-class MDM2 inhibitor, in neuroblastoma cell lines with different p53 backgrounds. The fin

SUBMITTER: Wang W 

PROVIDER: S-EPMC7762001 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature