Heterozygous mutations in valosin-containing protein (VCP) and resistance to VCP inhibitors.

ABSTRACT: In recent years, multiple studies including ours have reported on the mechanism of resistance towards valosin-containing protein (VCP) inhibitors. While all these studies reported target alterations via mutations in VCP as the primary mechanism of resistance, discrepancies persist to date regarding the zygosity of these mutations responsible for the resistance. In addition, the extent to which resistant cells harbor additional mutations in other genes is not well described. In this study, we performed global transcript analysis of the parental and previously reported VCP inhibitor (CB-5083) resistant cells and found additional mutations in the resistant cells. However, our CRISPR-Cas9 gene editing studies indicate that specific mutations in VCP are sufficient to produce resistance to CB-50

SUBMITTER: Bastola P 

PROVIDER: S-EPMC6662852 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature