SF3B1 mutations confer sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). Mechanistically, this is independent of homologous recombination repair and instead relies on a defective replication stress response due to a reduction of the cyclin-dependent kinase 2 interacting protein (CINP). PARPi treatment of SF3B1 mutant (SF3B1MUT) tumors leads to replication stress induced by increased fork origin firing and culminates in cell cycle stalling.
- Philip Bland
- Harry Saville
- Rachael Natrajan
