Understanding and overcoming resistance to PARP inhibitors in cancer therapy

被引:339
作者
Dias, Mariana Paes [1 ,2 ]
Moser, Sarah C. [1 ,2 ]
Ganesan, Shridar [3 ]
Jonkers, Jos [1 ,2 ]
机构
[1] Netherlands Canc Inst, Div Mol Pathol, Amsterdam, Netherlands
[2] Oncode Inst, Amsterdam, Netherlands
[3] Rutgers Canc Inst New Jersey, New Brunswick, NJ 08901 USA
基金
欧盟地平线“2020”;
关键词
POLY(ADP-RIBOSE) POLYMERASE PARP; NEGATIVE BREAST-CANCER; DOUBLE-STRAND BREAKS; CELL-FREE DNA; OLAPARIB MAINTENANCE THERAPY; REPLICATION FORK STABILITY; BRCA2 REVERSION MUTATIONS; SEROUS OVARIAN-CANCER; HOMOLOGOUS-RECOMBINATION; SYNTHETIC LETHALITY;
D O I
10.1038/s41571-021-00532-x
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Poly(ADP-ribose) polymerase (PARP) inhibitors are approved for patients with several forms of cancer, predominantly those harbouring loss-of-function BRCA1/2 mutations or other homologous recombination defects. Nonetheless, most patients receiving PARP inhibitors will ultimately develop resistance to PARP inhibitors, resulting in disease progression. In this Review, the authors describe the mechanisms of resistance to PARP inhibitors and discuss the potential treatment strategies that might overcome these effects. Developing novel targeted anticancer therapies is a major goal of current research. The use of poly(ADP-ribose) polymerase (PARP) inhibitors in patients with homologous recombination-deficient tumours provides one of the best examples of a targeted therapy that has been successfully translated into the clinic. The success of this approach has so far led to the approval of four different PARP inhibitors for the treatment of several types of cancers and a total of seven different compounds are currently under clinical investigation for various indications. Clinical trials have demonstrated promising response rates among patients receiving PARP inhibitors, although the majority will inevitably develop resistance. Preclinical and clinical data have revealed multiple mechanisms of resistance and current efforts are focused on developing strategies to address this challenge. In this Review, we summarize the diverse processes underlying resistance to PARP inhibitors and discuss the potential strategies that might overcome these mechanisms such as combinations with chemotherapies, targeting the acquired vulnerabilities associated with resistance to PARP inhibitors or suppressing genomic instability.
引用
收藏
页码:773 / 791
页数:19
相关论文
共 264 条
[71]   Rad52 inactivation is synthetically lethal with BRCA2 deficiency [J].
Feng, Zhihui ;
Scott, Shaun P. ;
Bussen, Wendy ;
Sharma, Girdhar G. ;
Guo, Gongshe ;
Pandita, Tej K. ;
Powell, Simon N. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2011, 108 (02) :686-691
[72]   SHLD2/FAM35A co-operates with REV7 to coordinate DNA double-strand break repair pathway choice [J].
Findlay, Steven ;
Heath, John ;
Luo, Vincent M. ;
Malina, Abba ;
Morin, Theo ;
Coulombe, Yan ;
Djerir, Billel ;
Li, Zhigang ;
Samiei, Arash ;
Simo-Cheyou, Estelle ;
Karam, Martin ;
Bagci, Halil ;
Rahat, Dolev ;
Grapton, Damien ;
Lavoie, Elise G. ;
Dove, Christian ;
Khaled, Husam ;
Kuasne, Hellen ;
Mann, Koren K. ;
Klein, Kathleen Oros ;
Greenwood, Celia M. ;
Tabach, Yuval ;
Park, Morag ;
Cote, Jean-Francois ;
Masson, Jean-Yves ;
Marechal, Alexandre ;
Orthwein, Alexandre .
EMBO JOURNAL, 2018, 37 (18)
[73]   Exploiting interconnected synthetic lethal interactions between PARP inhibition and cancer cell reversible senescence [J].
Fleury, Hubert ;
Malaquin, Nicolas ;
Tu, Veronique ;
Gilbert, Sophie ;
Martinez, Aurelie ;
Olivier, Marc-Alexandre ;
Sauriol, Alexandre ;
Communal, Laudine ;
Leclerc-Desaulniers, Kim ;
Carmona, Euridice ;
Provencher, Diane ;
Mes-Masson, Anne-Marie ;
Rodier, Francis .
NATURE COMMUNICATIONS, 2019, 10 (1)
[74]   Functional Radiogenetic Profiling Implicates ERCC6L2 in Non-homologous End Joining [J].
Francica, Paola ;
Mutlu, Merve ;
Blomen, Vincent A. ;
Oliveira, Catarina ;
Nowicka, Zuzanna ;
Trenner, Anika ;
Gerhards, Nora M. ;
Bouwman, Peter ;
Stickel, Elmer ;
Hekkelman, Maarten L. ;
Lingg, Lea ;
Klebic, Ismar ;
van de Ven, Marieke ;
de Korte-Grimmerink, Renske ;
Howald, Denise ;
Jonkers, Jos ;
Sartori, Alessandro A. ;
Fendler, Wojciech ;
Chapman, J. Ross ;
Brummelkamp, Thijn ;
Rottenberg, Sven .
CELL REPORTS, 2020, 32 (08)
[75]   Maintenance olaparib for patients (pts) with newly diagnosed, advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): 5-year (y) follow-up (f/u) from SOLO1 [J].
Friedlander, M. L. ;
Moore, K. ;
Colombo, N. ;
Scambia, G. ;
Kim, B-G. ;
Oaknin, A. ;
Lisyanskaya, A. ;
Floquet, A. ;
Leary, A. ;
Sonke, G. S. ;
Gourley, C. ;
Banerjee, S. ;
Oza, A. ;
Gonzalez-Martin, A. ;
Aghajanian, C. ;
Bradley, W. ;
Holmes, E. ;
Lowe, E. S. ;
Disilvestro, P. .
ANNALS OF ONCOLOGY, 2020, 31 :S1334-S1334
[76]   Pamiparib in combination with tislelizumab in patients with advanced solid tumours: results from the dose-escalation stage of a multicentre, open-label, phase 1a/b trial [J].
Friedlander, Michael ;
Meniawy, Tarek ;
Markman, Ben ;
Mileshkin, Linda ;
Harnett, Paul ;
Millward, Michael ;
Lundy, Joanne ;
Freimund, Alison ;
Norris, Christie ;
Mu, Song ;
Wu, John ;
Paton, Virginia ;
Gao, Bo .
LANCET ONCOLOGY, 2019, 20 (09) :1306-1315
[77]   Poly (ADP-Ribose) Polymerase Inhibitor Activity in Prostate Cancers Harboring Mutations in DNA Repair Genes: Who Benefits? [J].
Ganesan, Shridar ;
Garber, Judy .
JCO PRECISION ONCOLOGY, 2020, 4 :1034-1037
[78]   An OB-fold complex controls the repair pathways for DNA double-strand breaks [J].
Gao, Shengxian ;
Feng, Sumin ;
Ning, Shaokai ;
Liu, Jingyan ;
Zhao, Huayu ;
Xu, Yixi ;
Shang, Jinfeng ;
Li, Kejiao ;
Li, Qing ;
Guo, Rong ;
Xu, Dongyi .
NATURE COMMUNICATIONS, 2018, 9
[79]   53BP1 cooperation with the REV7-shieldin complex underpins DNA structure-specific NHEJ [J].
Ghezraoui, Hind ;
Oliveira, Catarina ;
Becker, Jordan R. ;
Bilham, Kirstin ;
Moralli, Daniela ;
Anzilotti, Consuelo ;
Fischer, Roman ;
Deobagkar-Lele, Mukta ;
Sanchiz-Calvo, Maria ;
Fueyo-Marcos, Elena ;
Bonham, Sarah ;
Kessler, Benedikt M. ;
Rottenberg, Sven ;
Cornall, Richard J. ;
Green, Catherine M. ;
Chapman, J. Ross .
NATURE, 2018, 560 (7716) :122-+
[80]   New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs [J].
Gibson, Bryan A. ;
Kraus, W. Lee .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2012, 13 (07) :411-424