Applying ⁸⁹Zr-Transferrin To Study the Pharmacology of Inhibitors to BET Bromodomain Containing Proteins.

ABSTRACT: Chromatin modifying proteins are attractive drug targets in oncology, given the fundamental reliance of cancer on altered transcriptional activity. Multiple transcription factors can be impacted downstream of primary target inhibition, thus making it challenging to understand the driving mechanism of action of pharmacologic inhibition of chromatin modifying proteins. This in turn makes it difficult to identify biomarkers predictive of response and pharmacodynamic tools to optimize drug dosing. In this report, we show that (89)Zr-transferrin, an imaging tool we developed to measure MYC activity in cancer, can be used to identify cancer models that respond to broad spectrum inhibitors of transcription primarily due to MYC inhibition. As a proof of concept, we studied inhibitors of BET bromod

SUBMITTER: Doran MG 

PROVIDER: S-EPMC4738321 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature