Identification of a Molecularly-Defined Subset of Breast and Ovarian Cancer Models that Respond to WEE1 or ATR Inhibition, Overcoming PARP Inhibitor Resistance.
Violeta SerraAnderson T WangMarta Castroviejo-BermejoUrszula M PolanskaMarta PalafoxAndrea Herencia-RoperoGemma N JonesZhongwu LaiJoshua ArmeniaFilippos MichopoulosAlba Llop-GuevaraRachel BroughAditi GulatiStephen J PettittKrishna C BulusuJenni NikkiläZena WilsonAdina M HughesPaul W G WijnhovenAmbar AhmedAlejandra BrunaAlbert Gris-OliverMarta GuzmanOlga RodríguezJudit GruesoJoaquín ArribasJavier CortesCristina SauraAlan LauSusan E CritchlowBrian DoughertyCarlos CaldasGordon B MillsJ Carl BarrettJosep V FormentElaine B CadoganChristopher J LordCristina CruzJudith BalmañaLenka Oplustil O'ConnorPublished in: Clinical cancer research : an official journal of the American Association for Cancer Research (2022)
Targeting the replication stress response is a valid therapeutic option to overcome PARPi resistance including tumors without an underlying HRR deficiency. These preclinical insights are now being tested in several clinical trials where the PARPi is administered with either the WEE1i or the ATRi.