biostudies-literatureMustafi SBankhead Coley Cancer Research ProgramFlight Attendant Medical Research InstituteNEI NIH HHSUniversity of Miami Sylvester Comprehensive Cancer CenterNINDS NIH HHSNCI NIH HHSNIH201-210https://www.ebi.ac.uk/biostudies/studies/S-EPMC6557781biostudies-literatureUnknown43<h4>Background</h4>Bromodomain and extra-terminal inhibitors (BETi) have shown efficacy for the treatment of aggressive triple negative breast cancer (TNBC). However, BETi are plagued by a narrow therapeutic window as manifested by severe toxicities at effective doses. Therefore, it is a limitation to their clinical implementation in patient care.<h4>Methods</h4>The impact of vitamin C on the efficacy of small compounds including BETi was assessed by high-throughput screening. Co-treatment of TNBC by BETi especially JQ1 and vitamin C was evaluated in vitro and in vivo.<h4>Findings</h4>High-throughput screening revealed that vitamin C improves the efficacy of a number of structurally-unrelated BETi including JQ1, I-BET762, I-BET151, and CPI-203 in treating TNBC cells. The synergy between BEEBioMedicineVitamin C supplementation expands the therapeutic window of BETi for triple negative breast cancer.PMC6557781R21CA191668T32 EY0231947BC101R56AG061911R21 CA191668R01 NS089525Camarena VHuff TCSant DWBrothers SPYoon HVolmar CHZheng LMustafi SQureshi RWang GWahlestedt CSlingerland JfalseVitamin C supplementation expands the therapeutic window of BETi for triple negative breast cancer.<h4>Background</h4>Bromodomain and extra-terminal inhibitors (BETi) have shown efficacy for the treatment of aggressive triple negative breast cancer (TNBC). However, BETi are plagued by a narrow therapeutic window as manifested by severe toxicities at effective doses. Therefore, it is a limitation to their clinical implementation in patient care.<h4>Methods</h4>The impact of vitamin C on the efficacy of small compounds including BETi was assessed by high-throughput screening. Co-treatment of TNBC by BETi especially JQ1 and vitamin C was evaluated in vitro and in vivo.<h4>Findings</h4>High-throughput screening revealed that vitamin C improves the efficacy of a number of structurally-unrelated BETi including JQ1, I-BET762, I-BET151, and CPI-203 in treating TNBC cells. The synergy between BE2019-01-01T00:00:00Z2019 May2025-04-04T22:09:09.662Z2019-07-24T07:13:52ZS-EPMC65577813097554410.1016/j.ebiom.2019.04.006