Therapeutically targeting oncogenic CRCs facilitates induced differentiation of NB by RA and the BET bromodomain inhibitor.

ABSTRACT: Retinoic acids (RAs) are the most successful therapeutics for cancer differentiation therapy used in high-risk neuroblastoma (NB) maintenance therapy but are limited in effectiveness. This study identifies a strategy for improving efficacy through disruption of cancer cell identity via BET inhibitors. Mutations that block development are theorized to cause NB through retention of immature cell identities contributing to oncogenesis. NB has two interchangeable cell identities, maintained by two different core transcriptional regulatory circuitries (CRCs): a therapy-resistant mesenchymal/stem cell state and a proliferative adrenergic cell state. MYCN amplification is a common mutation of high-risk NB and recently found to block differentiation by driving high expression of the adrenergic CRC

SUBMITTER: Alleboina S 

PROVIDER: S-EPMC8526497 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature