Toxic PARP Trapping upon cAMP-Induced DNA Damage Reinstates the Efficacy of Endocrine Therapy and CDK4/6 Inhibitors in Treatment-Refractory ER+ Breast Cancer

Scientists showed that standard of care therapy caused DNA damage and toxic PARP1 trapping upon generation of a functional BRCAness phenotype, leading to increased histone parylation and reduced H3K9 acetylation, resulting in transcriptional blockage and cell death.