Vitamin C supplementation expands the therapeutic window of BETi for triple negative breast cancer.

ABSTRACT:

Background

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.

Methods

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.

Findings

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 BE

SUBMITTER: Mustafi S 

PROVIDER: S-EPMC6557781 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature