PARP inhibitors in hereditary breast and ovarian cancer and other cancers: A review.

There has been a paradigm shift in the management of cancer, with the immense progress in cancer genomics. More and more targeted therapies are becoming available by the day and personalized medicine is becoming popular with specific drugs being designed for selected subgroups of patients. One such new class of targeted drugs in the armamentarium is Poly ADP Ribose Polymerase (PARP) inhibitors (PARPi), which inhibit the enzyme PARP, thus interfering with DNA repair. This strategy utilizes a pre-existing genomic lesion in tumors with homologous recombination repair defects (including BRCA mutations), weakening tumor cells further by blocking the alternate pathway of DNA repair. In this review, we discuss in detail, the evolution, genetics, mechanism of action, mechanism of resistance, indications of use of PARP inhibitors, as well as combination with other agents and future directions.