PARP inhibitors in the management of breast cancer: current data and future prospects.
Poly(ADP-ribose) polymerases (PARP) are enzymes involved in DNA-damage repair. Inhibition of PARPs is a promising strategy for targeting cancers with defective DNA-damage repair, including BRCA1 and BRCA2 mutation-associated breast and ovarian cancers. Several PARP inhibitors are currently in trials in the adjuvant, neoadjuvant, and metastatic settings for the treatment of ovarian, BRCA-mutated breast, and other cancers. We herein review the development of PARP inhibitors and the basis for the excitement surrounding these agents, their use as single agents and in combinations, as well as their toxicities, mechanisms of acquired resistance, and companion diagnostics.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. luca_livraghi@dfci.harvard.edu.
Luca
L
Livraghi
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. judy_garber@dfci.harvard.edu.
Judy E
JE
Garber
D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D004260:DNA Repair; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D009154:Mutation; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors