Splice-switch oligonucleotide-based combinatorial platform prioritizes synthetic lethal targets CHK1 and BRD4 against MYC-driven hepatocellular carcinoma.

ABSTRACT: Deregulation of MYC is among the most frequent oncogenic drivers in hepatocellular carcinoma (HCC). Unfortunately, the clinical success of MYC-targeted therapies is limited. Synthetic lethality offers an alternative therapeutic strategy by leveraging on vulnerabilities in tumors with MYC deregulation. While several synthetic lethal targets of MYC have been identified in HCC, the need to prioritize targets with the greatest therapeutic potential has been unmet. Here, we demonstrate that by pairing splice-switch oligonucleotide (SSO) technologies with our phenotypic-analytical hybrid multidrug interrogation platform, quadratic phenotypic optimization platform (QPOP), we can disrupt the functional expression of these targets in specific combinatorial tests to rapidly determine target-target i

SUBMITTER: Thng DKH 

PROVIDER: S-EPMC9842033 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature