Functional profiling of clear cell ovarian cancer. | 2012 ASCO Annual Meeting Abstracts

Functional profiling of clear cell ovarian cancer. | 2012 ASCO Annual Meeting Abstracts

Abstract:
Background: Clear cell ovarian cancer represents up to 15% of epithelial ovarian cancers. In comparison to other subtypes, clear cell ovarian carcinomas have a poorer prognosis and are relatively resistant to standard platinum based chemotherapy. Recently, loss of function mutations in the tumour suppressor gene ARID1A were identified in up to 50% of ovarian clear cell carcinomas. We have adopted an integral functional and molecular profiling approach as a route to identify new genetic dependencies and therapeutic targets for this disease.

Methods: Clear cell ovarian cancer cell lines were functionally profiled using high throughput screening with chemical and siRNA libraries. This has been integrated with molecular profiling data generated from exome and transcriptome sequencing to aid the discovery of novel targets.

Results: Using functional screens we have now identified critical gene dependencies and potential therapeutics in a series of clear cell ovarian cancer models. The comparison of functional viability profiles for models characterized by ARID1A loss of function mutations is now enabling an analysis of synthetic lethal effects that could be used to target clear cell ovarian cancers carrying these mutations.  

Conclusions: The work undertaken so far provides the framework for the discovery of therapeutic targets for clear cell ovarian cancer using an integrated approach. Revalidation of these preliminary results is now underway to characterize new genetic dependencies for this disease.