A novel mechanism to induce BRCAness in cancer cells

Cancer cells with germline deleterious mutations of BRCA1 or BRCA2 are deficient in homologous recombination repair and therefore sensitive to PARP inhibitor treatment. However, wild-type BRCA1/2-expressing cells with defects in other DNA damage repair pathway components may also exhibit “BRCAness,” which in combination with PARP inhibition can similarly induce synthetic lethality. In this issue of Cancer Research, Luo and colleagues report a novel mechanism by which BRCA1 protein degradation in response to DNA double-strand breaks is regulated by prolyl isomerase Pin1. Inactivation of Pin1 can establish BRCAness in cancer cells and thus sensitize cells to PARP inhibitor treatment.