Targeting IP6 signaling to destabilize homologous recombination proteins to overcome PARP inhibitor resistance - PubMed
4 hours ago
- #Cul4A-WDR5 pathway
- #PARP inhibitor resistance
- #homologous recombination
- ML367 and UNI418 inhibit PIKfyve and PIP5K1C, reducing IP6 levels.
- UNI418 triggers Cul4A-dependent degradation of RAD51, CtIP, and CHK1 via WDR5.
- This pathway suppresses homologous recombination and enhances PARP inhibitor sensitivity.
- UNI418 re-sensitizes PARPi-resistant tumors in in vitro and in vivo models.