A preclinical mouse model for targeted therapy in uterine leiomyosarcoma

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Sandra Orsulic, Ph.D.,  Cedars-Sinai Medical Center
Recipient of the: $25,000 research award, Shelby L. Richter Memorial Research Award

Uterine leiomyosarcoma (ULMS) is a rare gynecologic malignancy that has a low survival rate. Currently, there is no effective treatment for ULMS. We have generated a mouse model of ULMS and demonstrated that the loss of BRCA1 function accelerates the progression of these tumors. Consistent with the hypothesis that BRCA1 plays a role in ULMS, we have shown that the BRCA1 protein is absent in 36% of human ULMS. Our findings provide a rationale for investigating therapies that target BRCA1 deficiency in ULMS. To this end, we will determine the mechanism of BRCA1 downregulation in human tumor samples and test the efficacy of BRCA-targeted therapy in a mouse model of ULMS. The results of these studies could provide justification for a clinical trial for ULMS patients with a novel BRCA-targeted therapy based on poly(ADP-ribose)-polymerase-1 (PARP-1) inhibitors.