Synthetic Lethal Approaches Exploiting DNA Damage in Aggressive Myeloma.

ABSTRACT:

Unlabelled

Ongoing DNA damage is a common feature of epithelial cancers. Here, we show that tumor cells derived from multiple myeloma, a disease of clonal plasma cells, demonstrate DNA-replicative stress, leading to DNA damage. We identified a poor-prognosis subset of multiple myeloma with extensive chromosomal instability and replicative stress, which rely on ATR to compensate for DNA-replicative stress; conversely, silencing of ATR or treatment with a specific ATR inhibitor triggers multiple myeloma cell apoptosis. We show that oncogenes, such as MYC, induce DNA damage in multiple myeloma cells not only by increased replicative stress, but also via increased oxidative stress, and that reactive oxygen species-inducer piperlongumine triggers further DNA damage and apoptosis. Import

SUBMITTER: Cottini F 

PROVIDER: S-EPMC4560623 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature