Functional genomics identifies new synergistic therapies for retinoblastoma.

ABSTRACT: Local intravitreal or intra-arterial chemotherapy has improved therapeutic success for the pediatric cancer retinoblastoma (RB), but toxicity remains a major caveat. RB initiates primarily with RB1 loss or, rarely, MYCN amplification, but the critical downstream networks are incompletely understood. We set out to uncover perturbed molecular hubs, identify synergistic drug combinations to target these vulnerabilities, and expose and overcome drug resistance. We applied dynamic transcriptomic analysis to identify network hubs perturbed in RB versus normal fetal retina, and performed in vivo RNAi screens in RB1^null and RB1^wt;MYCN^amp orthotopic xenografts to pinpoint essential hubs. We employed in vitro and in vivo studies to validate hits, define mechanism, de

SUBMITTER: Aubry A 

PROVIDER: S-EPMC7391301 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature