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Review

Parp Inhibitors: The Journey from Research Hypothesis to Clinical Approval

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Pages 139-154 | Published online: 23 Mar 2015

References

  • Siegel R , NaishadhamD , JemalA . Cancer statistics, 2013 . CA Cancer J. Clin.63 ( 1 ), 11 – 30 ( 2013 ).
  • Jemal A , BrayF , CenterMM , FerlayJ , WardE , FormanD . Global cancer statistics . CA Cancer J. Clin.61 ( 2 ), 69 – 90 ( 2011 ).
  • Butler-Henderson K , LeeAH , PriceRI , WaringK . Intraoperative assessment of margins in breast conserving therapy: a systematic review . Breast23 ( 2 ), 112 – 119 ( 2014 ).
  • Weinstein IB , JoeA . Oncogene addiction . Cancer Res.68 ( 9 ), 3077 – 3080 ; discussion 3080 ( 2008 ).
  • Torti D , TrusolinoL . Oncogene addiction as a foundational rationale for targeted anti-cancer therapy: promises and perils . EMBO Mol. Med.3 ( 11 ), 623 – 636 ( 2011 ).
  • Druker BJ . Translation of the Philadelphia chromosome into therapy for CML . Blood112 ( 13 ), 4808 – 4817 ( 2008 ).
  • Campos SM , WinerEP . Hormonal therapy in postmenopausal women with breast cancer . Oncology64 ( 4 ), 289 – 299 ( 2003 ).
  • Madarnas Y , TrudeauM , FranekJA , MccreadyD , PritchardKI , MessersmithH . Adjuvant/neoadjuvant trastuzumab therapy in women with HER-2/neu-overexpressing breast cancer: a systematic review . Cancer Treat. Rev.34 ( 6 ), 539 – 557 ( 2008 ).
  • Chapman PB , HauschildA , RobertCet al. Improved survival with vemurafenib in melanoma with BRAF V600E mutation . N. Engl. J. Med.364 ( 26 ), 2507 – 2516 ( 2011 ).
  • Hauschild A , GrobJJ , DemidovLVet al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial . Lancet380 ( 9839 ), 358 – 365 ( 2012 ).
  • Dobzhansky T . Genetics of natural populations; recombination and variability in populations of Drosophila pseudoobscura . Genetics31 , 269 – 290 ( 1946 ).
  • Hartwell LH , SzankasiP , RobertsCJ , MurrayAW , FriendSH . Integrating genetic approaches into the discovery of anticancer drugs . Science278 ( 5340 ), 1064 – 1068 ( 1997 ).
  • Bryant HE , SchultzN , ThomasHDet al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase . Nature434 ( 7035 ), 913 – 917 ( 2005 ).
  • Farmer H , MccabeN , LordCJet al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy . Nature434 ( 7035 ), 917 – 921 ( 2005 ).
  • Kastan MB . DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture . Mol. Cancer Res.6 ( 4 ), 517 – 524 ( 2008 ).
  • O’sullivan CC , MoonDH , KohnEC , LeeJM . Beyond breast and ovarian cancers: PARP inhibitors for BRCA mutation-associated and BRCA-like solid Tumors . Front. Oncol.4 , 42 ( 2014 ).
  • Cheung-Ong K , GiaeverG , NislowC . DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology . Chem. Biol.20 ( 5 ), 648 – 659 ( 2013 ).
  • De Murcia G , Menissier De MurciaJ . Poly(ADP-ribose) polymerase: a molecular nick-sensor . Trends Biochem. Sci.19 ( 4 ), 172 – 176 ( 1994 ).
  • Murai J , HuangSY , DasBBet al. Trapping of PARP1 and PARP2 by clinical PARP Inhibitors . Cancer Res.72 ( 21 ), 5588 – 5599 ( 2012 ).
  • Plummer ER . Inhibition of poly(ADP-ribose) polymerase in cancer . Curr. Opin. Pharmacol.6 ( 4 ), 364 – 368 ( 2006 ).
  • Helleday T . The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings . Mol. Oncol.5 ( 4 ), 387 – 393 ( 2011 ).
  • Bethesda MD . National Library of Medicine (US) . ( 2000 ). http://clinicaltrials.gov/ .
  • Fong PC , BossDS , YapTAet al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers . N. Engl. J. Med.361 ( 2 ), 123 – 134 ( 2009 ).
  • Tutt A , RobsonM , GarberJEet al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial . Lancet376 ( 9737 ), 235 – 244 ( 2010 ).
  • Audeh MW , CarmichaelJ , PensonRTet al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial . Lancet376 ( 9737 ), 245 – 251 ( 2010 ).
  • Gelmon KA , TischkowitzM , MackayHet al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study . Lancet Oncol.12 ( 9 ), 852 – 861 ( 2011 ).
  • Kaye SB , LubinskiJ , MatulonisUet al. Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer . J. Clin. Oncol.30 ( 4 ), 372 – 379 ( 2012 ).
  • Bundred N , GardovskisJ , JaskiewiczJet al. Evaluation of the pharmacodynamics and pharmacokinetics of the PARP inhibitor olaparib: a phase I multicentre trial in patients scheduled for elective breast cancer surgery . Invest. New Drugs31 ( 4 ), 949 – 958 ( 2013 ).
  • SaMol J , RansonM , ScottEet al. Safety and tolerability of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib (AZD2281) in combination with topotecan for the treatment of patients with advanced solid tumors: a phase I study . Invest. New Drugs30 ( 4 ), 1493 – 1500 ( 2012 ).
  • Liu JF , TolaneySM , BirrerMet al. A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer . Eur. J. Cancer49 ( 14 ), 2972 – 2978 ( 2013 ).
  • Khan OA , GoreM , LoriganPet al. A phase I study of the safety and tolerability of olaparib (AZD2281, KU0059436) and dacarbazine in patients with advanced solid tumours . Br. J. Cancer104 ( 5 ), 750 – 755 ( 2011 ).
  • Dean E , MiddletonMR , PwintTet al. Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours . Br. J. Cancer106 ( 3 ), 468 – 474 ( 2012 ).
  • Rajan A , CarterCA , KellyRJet al. A phase I combination study of olaparib with cisplatin and gemcitabine in adults with solid tumors . Clin. Cancer Res.18 ( 8 ), 2344 – 2351 ( 2012 ).
  • Ledermann J , HarterP , GourleyCet al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer . N. Engl. J. Med.366 ( 15 ), 1382 – 1392 ( 2012 ).
  • Plummer R , JonesC , MiddletonMet al. Phase I study of the poly(ADP-ribose) polymerase inhibitor, AG014699, in combination with temozolomide in patients with advanced solid tumors . Clin. Cancer Res.14 ( 23 ), 7917 – 7923 ( 2008 ).
  • Plummer R , LoriganP , StevenNet al. A phase II study of the potent PARP inhibitor, Rucaparib (PF-01367338, AG014699), with temozolomide in patients with metastatic melanoma demonstrating evidence of chemopotentiation . Cancer Chemother. Pharmacol.71 ( 5 ), 1191 – 1199 ( 2013 ).
  • Mukhopadhyay A , ElattarA , CerbinskaiteAet al. Development of a functional assay for homologous recombination status in primary cultures of epithelial ovarian tumor and correlation with sensitivity to poly(ADP-ribose) polymerase inhibitors . Clin. Cancer Res.16 ( 8 ), 2344 – 2351 ( 2010 ).
  • Mukhopadhyay A , PlummerER , ElattarAet al. Clinicopathological features of homologous recombination-deficient epithelial ovarian cancers: sensitivity to PARP inhibitors, platinum, and survival . Cancer Res.72 ( 22 ), 5675 – 5682 ( 2012 ).
  • Kummar S , KindersR , GutierrezMEet al. Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies . J. Clin. Oncol.27 ( 16 ), 2705 – 2711 ( 2009 ).
  • Kummar S , ChenA , JiJet al. Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas . Cancer Res.71 ( 17 ), 5626 – 5634 ( 2011 ).
  • Kummar S , JiJ , MorganRet al. A phase I study of veliparib in combination with metronomic cyclophosphamide in adults with refractory solid tumors and lymphomas . Clin. Cancer Res.18 ( 6 ), 1726 – 1734 ( 2012 ).
  • Sandhu SK , SchelmanWR , WildingGet al. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a Phase 1 dose-escalation trial . Lancet Oncol.14 ( 9 ), 882 – 892 ( 2013 ).
  • Shen Y , RehmanFL , FengYet al. BMN 673, a novel and highly potent PARP1/2 inhibitor for the treatment of human cancers with DNA repair deficiency . Clin. Cancer Res.19 ( 18 ), 5003 – 5015 ( 2013 ).
  • Murai J , HuangSY , RenaudAet al. Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib . Mol. Cancer Ther.13 ( 2 ), 433 – 443 ( 2014 ).
  • O’shaughnessy J , OsborneC , PippenJEet al. Iniparib plus chemotherapy in metastatic triple-negative breast cancer . N. Engl. J. Med.364 ( 3 ), 205 – 214 ( 2011 ).
  • Sinha G . Downfall of iniparib: a PARP inhibitor that doesn’t inhibit PARP after all . J. Natl Cancer Inst.106 ( 1 ), djt447 ( 2014 ).
  • Patel AG , De LorenzoSB , FlattenKS , PoirierGG , KaufmannSH . Failure of iniparib to inhibit poly(ADP-Ribose) polymerase in vitro . Clin. Cancer Res.18 ( 6 ), 1655 – 1662 ( 2012 ).
  • Moore K , DiSilvestroP , LoweE , GarnettS , Pujade-LauraineE . SOLO1 and SOLO2: Randomized phase III trials of olaparib in patients with ovarian cancer and a BRCA1/2 mutation (BRCAm) . J. Clin. Oncol.32 ( 15 ), Abstract TPS5616 ( 2014 ).
  • Von Minckwitz G , O’ShaughnessyJ , WinerEet al. Phase III study evaluating safety and efficacy of the addition of veliparib plus carboplatin versus the addition of carboplatin to standard neoadjuvant chemotherapy in subjects with early-stage triple-negative breast cancer (TNBC) . J. Clin. Oncol.32 ( 15 ), Abstract TPS1149 ( 2014 ).
  • Moore K , ZhangZ , AgarwalSet al. Food effect substudy of a phase 3 randomized double-blind trial of maintenance with niraparib (MK4827), a poly(ADP)ribose polymerase (PARP) inhibitor versus placebo in patients with platinum-sensitive ovarian cancer . J. Clin. Oncol.32 ( 15 ), Abstract e16531 ( 2014 ).
  • Gupta SK , MladekAC , CarlsonBLet al. Discordant in vitro and in vivo chemopotentiating effects of the parp inhibitor veliparib in temozolomide-sensitive versus -resistant glioblastoma multiforme xenografts . Clin. Cancer Res.20 ( 14 ), 3730 – 3741 ( 2014 ).
  • Su JM , ThompsonP , AdesinaAet al. A phase I trial of veliparib (ABT-888) and temozolomide in children with recurrent CNS tumors: a Pediatric Brain Tumor Consortium report dagger . Neuro. Oncol.16 ( 12 ), 1661 – 1668 ( 2014 ).
  • Gonzalez-Angulo AM , TimmsKM , LiuSet al. Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer . Clin. Cancer Res.17 ( 5 ), 1082 – 1089 ( 2011 ).
  • Garg K , LevineDA , OlveraNet al. BRCA1 immunohistochemistry in a molecularly characterized cohort of ovarian high-grade serous carcinomas . Am J. Surg. Pathol.37 ( 1 ), 138 – 146 ( 2013 ).
  • Cai F , GeI , WangM , BiskupE , LinX , ZhongX . Pyrosequencing analysis of BRCA1 methylation level in breast cancer cells . Tumour Biol.35 ( 4 ), 3839 – 3844 ( 2014 ).
  • Turner N , TuttA , AshworthA . Hallmarks of ‘BRCAness’ in sporadic cancers . Nat. Rev. Cancer4 ( 10 ), 814 – 819 ( 2004 ).
  • Ibragimova I , CairnsP . Assays for hypermethylation of the BRCA1 gene promoter in tumor cells to predict sensitivity to PARP-inhibitor therapy . Methods Mol. Biol.780 , 277 – 291 ( 2011 ).
  • Veeck J , RoperoS , SetienFet al. BRCA1 CpG island hypermethylation predicts sensitivity to poly(adenosine diphosphate)-ribose polymerase inhibitors . J. Clin. Oncol.28 ( 29 ), e563 – e564 ; author reply e565–e566 ( 2010 ).
  • Stefansson OA , VillanuevaA , VidalA , MartiL , EstellerM . BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer . Epigenetics7 ( 11 ), 1225 – 1229 ( 2012 ).
  • Muggia F , SafraT . ‘BRCAness’ and its implications for platinum action in gynecologic cancer . Anticancer Res.34 ( 2 ), 551 – 556 ( 2014 ).
  • Oplustilova L , WolaninK , MistrikMet al. Evaluation of candidate biomarkers to predict cancer cell sensitivity or resistance to PARP-1 inhibitor treatment . Cell Cycle11 ( 20 ), 3837 – 3850 ( 2012 ).
  • Min A , ImSA , YoonYKet al. RAD51C-deficient cancer cells are highly sensitive to the PARP inhibitor olaparib . Mol. Cancer Ther.12 ( 6 ), 865 – 877 ( 2013 ).
  • Birkelbach M , FerraioloN , GheorghiuLet al. Detection of impaired homologous recombination repair in NSCLC cells and tissues . J. Thorac. Oncol.8 ( 3 ), 279 – 286 ( 2013 ).
  • Daemen A , WolfDM , KorkolaJEet al. Cross-platform pathway-based analysis identifies markers of response to the PARP inhibitor olaparib . Breast Cancer Res. Treat.135 ( 2 ), 505 – 517 ( 2012 ).
  • Gottipati P , VischioniB , SchultzNet al. Poly(ADP-ribose) polymerase is hyperactivated in homologous recombination-defective cells . Cancer Res.70 ( 13 ), 5389 – 5398 ( 2010 ).
  • Bajrami I , FrankumJR , KondeAet al. Genome-wide profiling of genetic synthetic lethality identifies CDK12 as a novel determinant of PARP1/2 inhibitor sensitivity . Cancer Res.74 ( 1 ), 287 – 297 ( 2014 ).
  • Mccabe N , TurnerNC , LordCJet al. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition . Cancer Res.66 ( 16 ), 8109 – 8115 ( 2006 ).
  • Minami D , TakigawaN , TakedaHet al. Synergistic effect of olaparib with combination of cisplatin on PTEN-deficient lung cancer cells . Mol. Cancer Res.11 ( 2 ), 140 – 148 ( 2013 ).
  • Postel-Vinay S , BajramiI , FribouletLet al. A high-throughput screen identifies PARP1/2 inhibitors as a potential therapy for ERCC1-deficient non-small cell lung cancer . Oncogene32 ( 47 ), 5377 – 5387 ( 2013 ).
  • Dedes KJ , WetterskogD , Mendes-PereiraAMet al. PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors . Sci. Transl. Med.2 ( 53 ), 53ra75 ( 2010 ).
  • Bailey ML , O’NeilNJ , Van PelDM , SolomonDA , WaldmanT , HieterP . Glioblastoma cells containing mutations in the cohesin component STAG2 are sensitive to PARP inhibition . Mol. Cancer Ther.13 ( 3 ), 724 – 732 ( 2014 ).
  • Garnett MJ , EdelmanEJ , HeidornSJet al. Systematic identification of genomic markers of drug sensitivity in cancer cells . Nature483 ( 7391 ), 570 – 575 ( 2012 ).
  • Flott S , KwonY , PigliYZ , RicePA , SungP , JacksonSP . Regulation of Rad51 function by phosphorylation . EMBO Rep12 ( 8 ), 833 – 839 ( 2011 ).
  • Neijenhuis S , BajramiI , MillerR , LordCJ , AshworthA . Identification of miRNA modulators to PARP inhibitor response . DNA Repair (Amsterdam)12 ( 6 ), 394 – 402 ( 2013 ).
  • Bebb DG , Lees-MillerSP . Predicting PARP inhibitor sensitivity and resistance . Cell Cycle11 ( 22 ), 4110 ( 2012 ).
  • Graeser M , MccarthyA , LordCJet al. A marker of homologous recombination predicts pathologic complete response to neoadjuvant chemotherapy in primary breast cancer . Clin. Cancer Res.16 ( 24 ), 6159 – 6168 ( 2010 ).
  • Naipal KA , VerkaikNS , AmezianeNet al. Functional ex vivo assay to select Homologous Recombination deficient breast tumors for PARP inhibitor treatment . Clin. Cancer Res.20 ( 18 ), 4816 – 4826 ( 2014 ).
  • Drew Y , MulliganEA , VongWTet al. Therapeutic potential of poly(ADP-ribose) polymerase inhibitor AG014699 in human cancers with mutated or methylated BRCA1 or BRCA2 . J. Natl Cancer Inst.103 ( 4 ), 334 – 346 ( 2011 ).
  • Miyasaka A , OdaK , IkedaYet al. Anti-tumor activity of olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, in cultured endometrial carcinoma cells . BMC Cancer14 , 179 ( 2014 ).
  • Larsen MJ , KruseTA , TanQet al. Classifications within molecular subtypes enables identification of BRCA1/BRCA2 mutation carriers by RNA tumor profiling . PLoS ONE8 ( 5 ), e64268 ( 2013 ).
  • Mcmullin RP , WittnerBS , YangCet al. A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity . Breast Cancer Res.16 ( 2 ), R25 ( 2014 ).
  • Ihara M , TakeshitaS , OkaichiK , OkumuraY , OhnishiT . Heat exposure enhances radiosensitivity by depressing DNA-PK kinase activity during double strand break repair . Int. J. Hyperthermia30 ( 2 ), 102 – 109 ( 2014 ).
  • Kukielka AM , HetnalM , DabrowskiTet al. Salvage prostate HDR brachytherapy combined with interstitial hyperthermia for local recurrence after radiation therapy failure . Strahlenther Onkol.190 ( 2 ), 165 – 170 ( 2014 ).
  • Genet SC , FujiiY , MaedaJet al. Hyperthermia inhibits homologous recombination repair and sensitizes cells to ionizing radiation in a time- and temperature-dependent manner . J. Cell. Physiol.228 ( 7 ), 1473 – 1481 ( 2013 ).
  • Bergs JW , KrawczykPM , BorovskiTet al. Inhibition of homologous recombination by hyperthermia shunts early double strand break repair to non-homologous end-joining . DNA Repair (Amsterdam)12 ( 1 ), 38 – 45 ( 2013 ).
  • Krawczyk PM , EppinkB , EssersJet al. Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly (ADP-ribose) polymerase-1 inhibition . Proc. Natl Acad. Sci. USA108 ( 24 ), 9851 – 9856 ( 2011 ).
  • Numan WC , HofstetterLW , KotekGet al. Exploration of MR-guided head and neck hyperthermia by phantom testing of a modified prototype applicator for use with proton resonance frequency shift thermometry . Int. J. Hyperthermia30 ( 3 ), 184 – 191 ( 2014 ).
  • Ha K , FiskusW , ChoiDSet al. Histone deacetylase inhibitor treatment induces ‘BRCAness’ and synergistic lethality with PARP inhibitor and cisplatin against human triple negative breast cancer cells . Oncotarget5 ( 14 ), 5637 – 5650 ( 2014 ).
  • Konstantinopoulos PA , WilsonAJ , SaskowskiJ , WassE , KhabeleD . Suberoylanilide hydroxamic acid (SAHA) enhances olaparib activity by targeting homologous recombination DNA repair in ovarian cancer . Gynecol. Oncol.133 ( 3 ), 599 – 606 ( 2014 ).
  • Edwards SL , BroughR , LordCJet al. Resistance to therapy caused by intragenic deletion in BRCA2 . Nature451 ( 7182 ), 1111 – 1115 ( 2008 ).
  • Sakai W , SwisherEM , KarlanBYet al. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers . Nature451 ( 7182 ), 1116 – 1120 ( 2008 ).
  • Swisher EM , SakaiW , KarlanBY , WurzK , UrbanN , TaniguchiT . Secondary BRCA1 mutations in BRCA1-mutated ovarian carcinomas with platinum resistance . Cancer Res.68 ( 8 ), 2581 – 2586 ( 2008 ).
  • Norquist B , WurzKA , PennilCCet al. Secondary somatic mutations restoring BRCA1/2 predict chemotherapy resistance in hereditary ovarian carcinomas . J. Clin. Oncol.29 ( 22 ), 3008 – 3015 ( 2011 ).
  • Jaspers JE , KersbergenA , BoonUet al. Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors . Cancer Discov.3 ( 1 ), 68 – 81 ( 2013 ).
  • Barber LJ , SandhuS , ChenLet al. Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor . J Pathol229 ( 3 ), 422 – 429 ( 2013 ).
  • Aly A , GanesanS . BRCA1, PARP, and 53BP1: conditional synthetic lethality and synthetic viability . J. Mol. Cell Biol.3 ( 1 ), 66 – 74 ( 2011 ).
  • Cao L , XuX , BuntingSFet al. A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency . Mol. Cell35 ( 4 ), 534 – 541 ( 2009 ).
  • Bunting SF , CallenE , KozakMLet al. BRCA1 functions independently of homologous recombination in DNA interstrand crosslink repair . Mol. Cell46 ( 2 ), 125 – 135 ( 2012 ).
  • Bouwman P , AlyA , EscandellJMet al. 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers . Nat. Struct. Mol. Biol.17 ( 6 ), 688 – 695 ( 2010 ).
  • Grotsky DA , Gonzalez-SuarezI , NovellAet al. BRCA1 loss activates cathepsin L-mediated degradation of 53BP1 in breast cancer cells . J. Cell. Biol.200 ( 2 ), 187 – 202 ( 2013 ).
  • Pennington KP , WickramanayakeA , NorquistBMet al. 53BP1 expression in sporadic and inherited ovarian carcinoma: relationship to genetic status and clinical outcomes . Gynecol. Oncol.128 ( 3 ), 493 – 499 ( 2013 ).
  • Watanabe S , WatanabeK , AkimovVet al. JMJD1C demethylates MDC1 to regulate the RNF8 and BRCA1-mediated chromatin response to DNA breaks . Nat. Struct. Mol. Biol.20 ( 12 ), 1425 – 1433 ( 2013 ).
  • Chapman JR , BarralP , VannierJBet al. RIF1 is essential for 53BP1-dependent nonhomologous end joining and suppression of DNA double-strand break resection . Mol. Cell49 ( 5 ), 858 – 871 ( 2013 ).
  • Johnson N , JohnsonSF , YaoWet al. Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance . Proc. Natl Acad. Sci. USA110 ( 42 ), 17041 – 17046 ( 2013 ).
  • Nakada S , YonamineRM , MatsuoK . RNF8 regulates assembly of RAD51 at DNA double-strand breaks in the absence of BRCA1 and 53BP1 . Cancer Res.72 ( 19 ), 4974 – 4983 ( 2012 ).
  • Choi YH , YuAM . ABC transporters in multidrug resistance and pharmacokinetics, and strategies for drug development . Curr. Pharm. Des.20 ( 5 ), 793 – 807 ( 2014 ).
  • Rottenberg S , JonkersJ . Modeling therapy resistance in genetically engineered mouse cancer models . Drug Resist. Updat.11 ( 1–2 ), 51 – 60 ( 2008 ).
  • Lawlor D , MartinP , BusschotsSet al. PARP inhibitors as P-glyoprotein substrates . J. Pharm. Sci.103 ( 6 ), 1913 – 1920 ( 2014 ).
  • FDA News Release . FDA approves Lynparza to treat advanced ovarian cancer . ( 2014 ). www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm427554.htm .
  • AstraZeneca Press Release . Lynparza™ approved in the European Union as first-in-class treatment foradvanced BRCA-mutated ovarian cancer . ( 2014 ). www.astrazeneca.com/Media/Press-releases/Article/20141218--lynparza-approved-in-the-european-union .

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