Differential DNA damage response to WRN inhibition identifies a targetable vulnerability in ARID1A-mutated cancers - PubMed
5 hours ago
- #WRN inhibition
- #DNA damage response
- #ARID1A mutation
- ARID1A mutations are common in cancers, but effective treatments are lacking.
- Inhibition of WRN selectively targets ARID1A-mutated cells through defective Chk1 signaling and compensatory Chk2 activation, causing G1 arrest and apoptosis.
- Combining WRN inhibition with p21 inhibition forces G1-arrested ARID1A-mutated cells to re-enter the cell cycle, leading to mitotic catastrophe and enhanced cell death.
- WRN inhibition alone and with p21 inhibition shows antitumor efficacy in xenograft models, identifying a targetable vulnerability.