Evaluating the therapeutic potential of ADAR1 inhibition for triple-negative breast cancer

Triple-negative breast cancer (TNBC) is the deadliest form of breast cancer. Unlike other types of breast cancer that can be effectively treated by targeted therapies, no such targeted therapy exists for all TNBC patients. The ADAR1 enzyme carries out A-to-I editing of RNA to prevent sensing of endogenous double-stranded RNAs. ADAR1 is highly expressed in breast cancer including TNBC. Here, we demonstrate that expression of ADAR1, specifically its p150 isoform, is required for the survival of TNBC cell lines. In TNBC cells, knockdown of ADAR1 attenuates proliferation and tumorigenesis. Moreover, ADAR1 knockdown leads to robust translational repression. ADAR1-dependent TNBC cell lines also exhibit elevated IFN stimulated gene expression. IFNAR1 reduction significantly rescued the proliferative defects of ADAR1 loss. These findings establish ADAR1 as a novel therapeutic target for TNBC tumors.

Automated summary

Triple-negative breast cancer (TNBC) is the deadliest form of breast cancer with no targeted therapy available. The ADAR1 enzyme, highly expressed in TNBC, is essential for the survival of TNBC cell lines. Knockdown of ADAR1 in TNBC cells attenuates proliferation and tumorigenesis, leading to translational repression and elevated IFN stimulated gene expression. These findings establish ADAR1 as a novel therapeutic target for TNBC tumors.