PARP inhibitors in the management of breast cancer: current data and future prospects

被引:206
作者
Livraghi, Luca [1 ]
Garber, Judy E. [1 ]
机构
[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA
关键词
BRCA; Breast cancer; PARP inhibitors; Poly(ADP-ribose) polymerases; POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; RECOMBINATION DEFICIENCY HRD; RECURRENT EPITHELIAL OVARIAN; REFRACTORY SOLID TUMORS; PHASE-1; DOSE-ESCALATION; EPOTHILONE-B ANALOG; II CLINICAL-TRIAL; DNA-REPAIR DEFECT; BRCA MUTANT-CELLS; HOMOLOGOUS RECOMBINATION;
D O I
10.1186/s12916-015-0425-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
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页数:16
相关论文
共 127 条
[1]  
AbbVie, STUD EV SAF EFF ADD
[2]  
Abbvie, STUD EV VEL SINGL AG
[3]  
AbbVie, 2015, STUD EV EFF TOL VEL
[4]  
AbbVie, PHAS 3 RAND PLAC CON
[5]   The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks [J].
Ali, Ammar A. E. ;
Timinszky, Gyula ;
Arribas-Bosacoma, Raquel ;
Kozlowski, Marek ;
Hassa, Paul O. ;
Hassler, Markus ;
Ladurner, Andreas G. ;
Pearl, Laurence H. ;
Oliver, Antony W. .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2012, 19 (07) :685-+
[6]   The PARP superfamily [J].
Amé, JC ;
Spenlehauer, C ;
de Murcia, G .
BIOESSAYS, 2004, 26 (08) :882-893
[7]   Efficacy of Chemotherapy in BRCA1/2 Mutation Carrier Ovarian Cancer in the Setting of PARP Inhibitor Resistance: A Multi-Institutional Study [J].
Ang, Joo Ern ;
Gourley, Charlie ;
Powell, C. Bethan ;
High, Hilda ;
Shapira-Frommer, Ronnie ;
Castonguay, Vincent ;
De Greve, Jacques ;
Atkinson, Tina ;
Yap, Timothy A. ;
Sandhu, Shahneen ;
Banerjee, Susana ;
Chen, Lee-May ;
Friedlander, Michael L. ;
Kaufman, Bella ;
Oza, Amit M. ;
Matulonis, Ursula ;
Barber, Louise J. ;
Kozarewa, Iwanka ;
Fenwick, Kerry ;
Assiotis, Ioannis ;
Campbell, James ;
Chen, Lina ;
de Bono, Johann S. ;
Gore, Martin E. ;
Lord, Christopher J. ;
Ashworth, Alan ;
Kaye, Stan B. .
CLINICAL CANCER RESEARCH, 2013, 19 (19) :5485-5493
[8]  
[Anonymous], SAN ANTONIO BREAST C
[9]  
Appleman LJ, 2012, J CLIN ONCOL, V30
[10]  
*ASTRAZENECA, OL ADJ TREATM PAT GE