Chlorambucil targets BRCA1/2-deficient tumours and counteracts PARP inhibitor resistance

ABSTRACT: Due to compromised homologous recombination (HR) repair, BRCA1- and BRCA2-mutated tumours accumulate DNA damage and genomic rearrangements conducive of tumour progression. To identify drugs that target specifically BRCA2-deficient cells, we screened a chemical library containing clinically used compounds. The top hit was chlorambucil, a bi-functional alkylating agent used for the treatment of chronic lymphocytic leukemia (CLL). We establish that chlorambucil is specifically toxic to BRCA1/2-deficient cells, including olaparib-resistant and cisplatin-resistant ones, suggesting the potential clinical use of chlorambucil against disease which is resistant to these drugs. Additionally, chlorambucil eradicates BRCA2-deficient xenografts and inhibits growth of olaparib-resistant patient-derived

SUBMITTER: Dr. Eliana Tacconi 

PROVIDER: S-SCDT-EMM-2018-09982 | biostudies-other |

REPOSITORIES: biostudies-other