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.
An ovarian cancer blog which includes quality resource materials: education, research, social networking, genetics and (some) healthcare politics.
“Not everything that can be counted counts and not everything that counts can be counted.”
Albert Einstein
This posting is somewhat similar to one that you ended up posting months later, on October 9, 2012 about the "British Journal of Cancer - Individuality in FGF1 expression significantly influences platinum resistance and progression-free survival in ovarian cancer." Both were cell-line studies, but still, it was gratifying to see that someone is picking up on the "functional profiling" moniker.
ReplyDeletehttp://ovariancancerandus.blogspot.com/2012/10/british-journal-of-cancer-individuality.html#.UIB-WGl25AQ
http://cancerfocus.org/forum/showthread.php?t=3702
as always, thanks for staying with us over the many years and importantly contributing your expertise
ReplyDelete