PARP inhibitors are considered promising anticancer agents and currently being tested in clinical trials in hereditary breast cancer patients harboring mutations in BRCA1 and BRCA2 genes.
Here, we use a genetically engineered mouse model of BRCA2-associated hereditary breast cancer to study drug resistance to several types of chemotherapy and PARP inhibition.
Rarity of "second-hit" inactivation of the involved gene in CHEK2-, NBN/NBS1- and BLM-associated BC demonstrates their substantial biological difference from BRCA1/2-driven cancers and makes them poorly suitable for the clinical trials with cisplatin and PARP inhibitors.
Loss of BRCA1 in sporadic breast cancer suggests that therapeutics targeting BRCA1 pathway in hereditary breast cancer like PARP inhibitors might be used as therapeutic targets for sporadic breast tumours.