Ovarian Cancer: BRCA genetics reveals targets for new therapies.

Ovarian cancer is the most lethal gynecological malignancy and the fifth cause of cancer mortality in women in the Western Countries. Advanced genomic analysis showed that most hereditary and a large proportion of sporadic ovarian cancers are associated with genetic and epigenetic aberrations either in BRCA1 and/or BRCA2 genes or in other genes involved in DNA repair and genomic stability. BRCA dysfunction identifies a major subset of ovarian cancers with peculiar epidemiological and clinical features, such as higher incidence in younger females, high-grade serous phenotype, better chemosensitivity and outcome. Being particularly sensitive to DNA-damaging agents, such as platinum compounds, these tumors are suitable for new therapeutic options that represent future challenges for oncologists. In this article we review the known molecular dysfunction in hereditary ovarian cancers and BRCAness and discuss the implications of new advances for more personalized treatments.