Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer.

ABSTRACT:

Background

The majority of BRCA1-mutant breast cancers are characterized by a triple-negative phenotype and a basal-like molecular subtype, associated with aggressive clinical behavior. Current treatment options are limited, highlighting the need for the development of novel targeted therapies for this tumor subtype.

Methods

Our group previously showed that EZH2 is functionally relevant in BRCA1-deficient breast tumors and blocking EZH2 enzymatic activity could be a potent treatment strategy. To validate the role of EZH2 as a therapeutic target and to identify new synergistic drug combinations, we performed a high-throughput drug combination screen in various cell lines derived from BRCA1-deficient and -proficient mouse mammary tumors.

Results

We identified the combin

SUBMITTER: Ratz L 

PROVIDER: S-EPMC9206299 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature