Aurora A Kinase Inhibition Is Synthetic Lethal With the Activation of MYCN in Retinoblastoma.

ABSTRACT:

Purpose

RB1 inactivation and MYCN activation have been documented as common oncogenic alterations in retinoblastoma (RB). Direct targeting of RB1 and MYCN has not yet been proven to be feasible. The current treatment options for RB mainly consist of conventional chemotherapy, which inevitably poses health-threatening side effects. Here, we aimed to screen an in-house compound library to identify potential drugs for the treatment of human RB.

Methods

Aurora A kinase (AURKA) inhibitors were identified by differential viability screening with a tool compound library, and the pharmacological safety and efficacy of candidate drugs were further validated in zebrafish and RB patient-derived xenograft (PDX) models in vivo. Further CUT & Tag assay, ChIP-qPCR and RNA seq performances

SUBMITTER: Liao Q 

PROVIDER: S-EPMC11809451 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature