New manuscript: PARG inhibitors part 2
Updated: Jul 20, 2020
Delighted to bring you a hot-off-the-press story, a manuscript that we have deposited on Biorxiv. Dr Cam Coulson-Gilmer, a post-doc in the team, has performed a detailed characterisation of 10 ovarian cancer cell lines in response to a PARG inhibitor, segregating them into six that are resistant and four are sensitive. Cam shows that sensitivity correlates with several markers of persistent DNA replication stress, and using Nanostring technology she shows that the PARGi-sensitive cell lines have down-regulated DNA replication genes.
This story builds upon our 2019 Cancer Cell paper and is a continuation of our collaboration with the CRUK Manchester Institute's Drug Discovery Unit. These observations suggest that a subset of HGSOC may respond to PARG inhibitors and that "replication stress" gene expression signature could serve as a predictive biomarker to guide the design of clinical trials.
I particularly like this figure, it's a 4 parameter plot and you can see the six resistant cell lines in the bottom left corner, all with low replication stress scores.