Targeting centrosomes in uterine leiomyosarcoma
Uterine leiomyosarcoma (ULMS) is characterized by its early metastases, frequent recurrences and poor outcome. Using genome-wide transcriptional profiling, we have found that the Aurora A and B centrosomal kinases are robustly overexpressed in ULMS.
1. Assess the clinical significance of Aurora kinase misexpression by correlating levels of expression and surrogates for function with outcome.
2. Determine the biologic impact of targeting Aurora kinases in ULMS using unique cell lines and a novel xenograft model in mice.
This work will determine whether a phase I/II trial of Aurora kinase inhibitors currently in clinical testing is warranted for ULMS patients.