Homologous recombination deficiency and hemizygosity drive resistance in breast cancer - PubMed
12 hours ago
- #breast cancer
- #therapy resistance
- #homologous recombination deficiency
- Germline and somatic oncogenic alterations co-occur in breast cancer, influencing tumor evolution and therapy resistance.
- Germline BRCA2-associated tumors are predisposed to RB1 loss-of-function alterations, leading to resistance to CDK4/6 inhibitors.
- RB1 hemizygosity and homologous recombination deficiency facilitate RB1 loss under CDK4/6 inhibitor pressure.
- PARP inhibition outperforms CDK4/6 inhibitors in preclinical models and clinical data for gBRCA2 carriers.
- A predictive framework is proposed for forecasting drug-resistant trajectories based on pre-treatment allelic configuration and mutational signatures.