Targeting the centriolar replication factor STIL synergizes with DNA damaging agents for treatment of ovarian cancer.

ABSTRACT: Advanced ovarian cancer is an incurable disease. Thus, novel therapies are required. We wished to identify new therapeutic targets for ovarian cancer. ShRNA screen performed in 42 ovarian cancer cell lines identified the centriolar replication factor STIL as an essential gene for ovarian cancer cells. This was verified in-vivo in orthotopic human ovarian cancer mouse models. STIL depletion by administration of siRNA in neutral liposomes resulted in robust anti-tumor effect that was further enhanced in combination with cisplatin. Consistent with this finding, STIL depletion enhanced the extent of DNA double strand breaks caused by DNA damaging agents. This was associated with centrosomal depletion, ongoing genomic instability and enhanced formation of micronuclei. Interestingly, the ongoing

SUBMITTER: Rabinowicz N 

PROVIDER: S-EPMC5432342 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature