Synthetic lethality between PBRM1 deficiency and PARP inhibitors: exploiting G2/M checkpoint arrest in colorectal cancer - PubMed
5 hours ago
- #synthetic lethality
- #PARP inhibitors
- #colorectal cancer
- PBRM1 deficiency, commonly lost or mutated in cancers, lacks targeted treatments.
- PARP inhibitors show selective hypersensitivity in PBRM1-deficient colorectal cancer cells, inducing DNA damage, G2/M arrest, and apoptosis.
- Mechanistic studies using CRISPR-edited HCT116 cells confirm synthetic lethality, validated by viability and colony-formation assays.
- The sensitivity to PARP inhibitors is context-dependent and not uniform across all PBRM1-deficient models.
- PBRM1 may serve as a predictive biomarker in specific contexts, rather than a universal marker for PARP inhibitor response.