Exploiting the DNA Repair Defect in BRCA Mutant Cells in the Design of New Therapeutic Strategies for Cancer

Abstract

Individuals harboring germ-line mutations in the BRCA1 or BRCA2 genes are at highly elevated risk of a variety of cancers.Ten years of research has revealed roles for BRCA1 and BRCA2 in a wide variety of cellular processes. However, it seemslikely that the function of these proteins in DNA repair is critically important in maintaining genome stability. Despite thisincreasing knowledge of the defects present in BRCA-deficient cells, BRCA mutation carriers developing cancer are stilltreated similarly to sporadic cases. Here we describe our efforts, based on understanding the DNA repair defects in BRCAdeficientcells, to define the optimal existing treatment for cancers arising in BRCA mutation carriers and, additionally, thedevelopment of novel therapeutic approaches. Finally, we discuss how therapies developed to treat BRCA mutant tumorsmight be applied to some sporadic cancers sharing similar specific defects in DNA repair.