PARP inhibition radiosensitizes BRCA1 wildtype and mutated breast cancer to proton therapy.

ABSTRACT: Aggressive breast cancers often fail or acquire resistance to radiotherapy. To develop new strategies to improve the outcome of aggressive breast cancer patients, we studied how PARP inhibition radiosensitizes breast cancer models to proton therapy, which is a radiotherapy modality that generates more DNA damage in the tumor than standard radiotherapy using photons. Two human BRCA1-mutated breast cancer cell lines and their isogenic BRCA1-recovered pairs were treated with a PARP inhibitor and irradiated with photons or protons. Protons (9.9 and 3.85 keV/µm) induced higher cell kill independent of BRCA1 status. PARP inhibition amplified the cell kill effect to both photons and protons (9.9 and 3.85 keV/µm) independent of BRCA1 status. Numbers of γH2AX foci, micronuclei, and cGAS-positive mi

SUBMITTER: Ben Kacem M 

PROVIDER: S-EPMC11680706 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature