CRISPR/Cas9-mediated mutagenesis to validate the synergy between PARP1 inhibition and chemotherapy in BRCA1-mutated breast cancer cells.

ABSTRACT: For patients carrying BRCA1 mutations, at least one-third develop triple negative breast cancer (TNBC). Not only is TNBC difficult to treat due to the lack of molecular target receptors, but BRCA1 mutations (BRCA1m) also result in chemotherapeutic resistance, making disease recurrence more likely. Although BRCA1m are highly heterogeneous and therefore difficult to target, BRCA1 gene's synthetic lethal pair, PARP1, is conserved in BRCA1m cancer cells. Therefore, we hypothesize that targeting PARP1 might be a fruitful direction to sensitize BRCA1m cancer cells to chemotherapy. We used CRISPR/Cas9 technology to generate PARP1 deficiency in two TNBC cell lines, MDA-MB-231 (BRCA1 wild-type) and MDA-MB-436 (BRCA1m). We explored whether this PAR

SUBMITTER: Mintz RL 

PROVIDER: S-EPMC6971465 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature