Systematic screening identifies ABCG2 as a critical factor underlying synergy of kinase inhibitors

New publication online today!

With support from ScreeninC, Vera van der Noord and colleagues concluded a whole-genome CRISPR knockout screen and identified several genes that upon knockout sensitize Hs578T cells to treatment with THZ531, a CDK12/13 inhibitor. Among the genes identified was ABCG2. The authors found that ABCG2 mRNA expression correlated with the observation of synergy between THZ531 and kinase inhibitors. The authors then go on to demonstrate that ABCG2 plays a critical role in limiting the efficacy of CDK inhibitors and that multiple kinase inhibitors disrupt ABCG2 transporter function and thereby sensitize cells to CDK inhibitors.

The results of this project have been published in Breast Cancer Research.