1932

Abstract

Inhibitors of poly(ADP-ribose) polymerase (PARP) have recently entered the clinic for the treatment of homologous recombination–deficient cancers. Despite the success of this approach, resistance to PARP inhibitors (PARPis) is a clinical hurdle, and it is poorly understood how cancer cells escape the deadly effects of PARPis without restoring BRCA1/2 function. By synergizing the advantages of next-generation sequencing with functional genetic screens in tractable model systems, novel mechanisms providing useful insights into DNA damage response (DDR) have been identified. BRCA1/2 models not only are tools to explore therapy escape mechanisms but also yield basic knowledge about DDR pathways and PARPis’ mechanism of action. Moreover, alterations that render cells resistant to targeted therapies may cause new synthetic dependencies that can be exploited to combat resistant disease.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cancerbio-030617-050232
2019-03-04
2024-12-11
Loading full text...

Full text loading...

/deliver/fulltext/cancerbio/3/1/annurev-cancerbio-030617-050232.html?itemId=/content/journals/10.1146/annurev-cancerbio-030617-050232&mimeType=html&fmt=ahah

Literature Cited

  1. Afghahi A, Timms KM, Vinayak S, Jensen KC, Kurian AW et al. 2017. Tumor BRCA1 reversion mutation arising during neoadjuvant platinum-based chemotherapy in triple-negative breast cancer is associated with therapy resistance. Clin. Cancer Res. 23:133365–70
    [Google Scholar]
  2. Amé J-C, Fouquerel E, Gauthier LR, Biard D, Boussin FD et al. 2009. Radiation-induced mitotic catastrophe in PARG-deficient cells. J. Cell Sci. 122:Pt. 121990–2002
    [Google Scholar]
  3. Ang JE, Gourley C, Powell CB, High H, Shapira-Frommer R et al. 2013. Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study. Clin. Cancer Res. 19:195485–93
    [Google Scholar]
  4. Annunziato S, Barazas M, Rottenberg S, Jonkers J 2016. Genetic dissection of cancer development, therapy response, and resistance in mouse models of breast cancer. Cold Spring Harb. Symp. Quant. Biol. 81:141–141
    [Google Scholar]
  5. Bajrami I, Frankum JR, Konde A, Miller RE, Rehman FL et al. 2014. Genome-wide profiling of genetic synthetic lethality identifies CDK12 as a novel determinant of PARP1/2 inhibitor sensitivity. Cancer Res 74:1287–97
    [Google Scholar]
  6. Barazas M, Annunziato S, Pettitt SJ, de Krijger I, Ghezraoui H et al. 2018. The CST complex mediates end-protection at double-strand breaks and promotes PARP inhibitor sensitivity in BRCA1-deficient cells. Cell Rep 23:72107–18
    [Google Scholar]
  7. Barazas M, Gasparini A, Huang Y, Küçükosmanoğlu A, Annunziato S et al. 2018. Radiosensitivity is an acquired vulnerability of PARPi-resistant BRCA1-deficient tumors. Cancer Res In press
    [Google Scholar]
  8. Barber LJ, Sandhu S, Chen L, Campbell J, Kozarewa I et al. 2013. Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor. J. Pathol. 229:3422–29
    [Google Scholar]
  9. Barretina J, Caponigro G, Stransky N, Venkatesan K, Margolin AA et al. 2012. The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity. Nature 483:7391603–7
    [Google Scholar]
  10. Berti M, Ray Chaudhuri A, Thangavel S, Gomathinayagam S, Kenig S et al. 2013. Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition. Nat. Struct. Mol. Biol. 20:3347–54
    [Google Scholar]
  11. Bitler BG, Watson ZL, Wheeler LJ, Behbakht K 2017. PARP inhibitors: clinical utility and possibilities of overcoming resistance. Gynecol. Oncol. 147:3695–704
    [Google Scholar]
  12. Blackford AN, Jackson SP 2017. ATM, ATR, and DNA-PK: the trinity at the heart of the DNA damage response. Mol. Cell 66:6801–17
    [Google Scholar]
  13. Boersma V, Moatti N, Segura-Bayona S, Peuscher MH, van der Torre J et al. 2015. MAD2L2 controls DNA repair at telomeres and DNA breaks by inhibiting 5′ end resection. Nature 521:7553537–40
    [Google Scholar]
  14. Borst P, Evers R, Kool M, Wijnholds J 2000. A family of drug transporters: the multidrug resistance-associated proteins. J. Natl. Cancer Inst. 92:161295–302
    [Google Scholar]
  15. Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J et al. 2010. 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat. Struct. Mol. Biol. 17:6688–688
    [Google Scholar]
  16. Brown JS, Kaye SB, Yap TA 2016. PARP inhibitors: the race is on. Br. J. Cancer 114:7713–15
    [Google Scholar]
  17. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D et al. 2005. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434:7035913–17
    [Google Scholar]
  18. Bunting SF, Callén E, Wong N, Chen H-T, Polato F et al. 2010. 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141:2243–54
    [Google Scholar]
  19. Callaghan R, Luk F, Bebawy M 2014. Inhibition of the multidrug resistance P-glycoprotein: Time for a change of strategy. Drug Metab. Dispos. Biol. Fate Chem. 42:4623–31
    [Google Scholar]
  20. Callen E, Di Virgilio M, Kruhlak MJ, Nieto-Soler M, Wong N et al. 2013. 53BP1 mediates productive and mutagenic DNA repair through distinct phosphoprotein interactions. Cell 153:61266–80
    [Google Scholar]
  21. Cancer Genome Atlas Res. Netw. 2011. Integrated genomic analyses of ovarian carcinoma. Nature 474:7353609–15
    [Google Scholar]
  22. Cantor SB, Calvo JA 2018. Fork protection and therapy resistance in hereditary breast cancer. Cold Spring Harb. Symp. Quant. Biol. 82:339–48
    [Google Scholar]
  23. Cao L, Xu X, Bunting SF, Liu J, Wang RH et al. 2009. A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency. Mol. Cell 35:4534–41
    [Google Scholar]
  24. Ceccaldi R, Liu JC, Amunugama R, Hajdu I, Primack B et al. 2015. Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair. Nature 518:7538258–62
    [Google Scholar]
  25. Chao OS, Goodman OB 2014. Synergistic loss of prostate cancer cell viability by coinhibition of HDAC and PARP. Mol. Cancer Res. 12:121755–66
    [Google Scholar]
  26. Chapman JR, Barral P, Vannier J-B, Borel V, Steger M et al. 2013. RIF1 is essential for 53BP1-dependent nonhomologous end joining and suppression of DNA double-strand break resection. Mol. Cell 49:5858–71
    [Google Scholar]
  27. Chapman JR, Taylor MRG, Boulton SJ 2012. Playing the end game: DNA double-strand break repair pathway choice. Mol. Cell 47:4497–510
    [Google Scholar]
  28. Choi YE, Battelli C, Watson J, Liu J, Curtis J et al. 2014. Sublethal concentrations of 17-AAG suppress homologous recombination DNA repair and enhance sensitivity to carboplatin and olaparib in HR proficient ovarian cancer cells. Oncotarget 5:92678–87
    [Google Scholar]
  29. Christie EL, Fereday S, Doig K, Pattnaik S, Dawson S-J, Bowtell DDL 2017. Reversion of BRCA1/2 germline mutations detected in circulating tumor DNA from patients with high-grade serous ovarian cancer. J. Clin. Oncol. 35:121274–80
    [Google Scholar]
  30. Cortez D. 2015. Preventing replication fork collapse to maintain genome integrity. DNA Repair 32:149–57
    [Google Scholar]
  31. Dev H, Chiang T-WW, Lescale C, de Krijger I, Martin AG et al. 2018. Shieldin complex promotes DNA end-joining and counters homologous recombination in BRCA1-null cells. Nat. Cell Biol. 20:8954–65
    [Google Scholar]
  32. Di Virgilio M, Callen E, Yamane A, Zhang W, Jankovic M et al. 2013. Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching. Science 339:6120711–15
    [Google Scholar]
  33. Ding X, Ray Chaudhuri A, Callen E, Pang Y, Biswas K et al. 2016. Synthetic viability by BRCA2 and PARP1/ARTD1 deficiencies. Nat. Commun. 7:12425
    [Google Scholar]
  34. Dobzhansky T. 1946. Genetics of natural populations; recombination and variability in populations of Drosophila pseudoobscura. Genetics 31:269–90
    [Google Scholar]
  35. Dréan A, Lord CJ, Ashworth A 2016. PARP inhibitor combination therapy. Crit. Rev. Oncol. Hematol. 108:73–85
    [Google Scholar]
  36. Duarte AA, Gogola E, Sachs N, Barazas M, Annunziato S et al. 2018. BRCA-deficient mouse mammary tumor organoids to study cancer-drug resistance. Nat. Methods 15:2134–40
    [Google Scholar]
  37. Edwards SL, Brough R, Lord CJ, Natrajan R, Vatcheva R et al. 2008. Resistance to therapy caused by intragenic deletion in BRCA2. Nature 451:71821111–15
    [Google Scholar]
  38. Escribano-Díaz C, Orthwein A, Fradet-Turcotte A, Xing M, Young JTF et al. 2013. A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice. Mol. Cell 49:5872–83
    [Google Scholar]
  39. Evans T, Matulonis U 2017. PARP inhibitors in ovarian cancer: evidence, experience and clinical potential. Ther. Adv. Med. Oncol. 9:4253–67
    [Google Scholar]
  40. Farmer H, McCabe N, Lord CJ, Tutt ANJ, Johnson DA et al. 2005. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434:7035917–21
    [Google Scholar]
  41. Feng FY, Speers C, Liu M, Jackson WC, Moon D et al. 2014. Targeted radiosensitization with PARP1 inhibition: optimization of therapy and identification of biomarkers of response in breast cancer. Breast Cancer Res. Treat. 147:181–94
    [Google Scholar]
  42. Feng L, Fong K-W, Wang J, Wang W, Chen J 2013. RIF1 counteracts BRCA1-mediated end resection during DNA repair. J. Biol. Chem. 288:1611135–43
    [Google Scholar]
  43. Ferro AM, Olivera BM 1982. Poly(ADP-ribosylation) in vitro. Reaction parameters and enzyme mechanism. J. Biol. Chem. 257:137808–13
    [Google Scholar]
  44. Geenen JJJ, Linn SC, Beijnen JH, Schellens JHM 2018. PARP Inhibitors in the treatment of triple-negative breast cancer. Clin. Pharmacokinet. 57:4427–37
    [Google Scholar]
  45. Ghezraoui H, Oliveira C, Becker JR, Bilham K, Moralli D et al. 2018. 53BP1 cooperation with the REV7-shieldin complex underpins DNA structure-specific NHEJ. Nature 560:7716122–27
    [Google Scholar]
  46. Gibson BA, Kraus WL 2012. New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat. Rev. Mol. Cell Biol. 13:7411–24
    [Google Scholar]
  47. Gogola E, Duarte AA, de Ruiter JR, Wiegant WW, Schmid JA et al. 2018. Selective loss of PARG restores PARylation and counteracts PARP inhibitor-mediated synthetic lethality. Cancer Cell 33:61078–93.e12
    [Google Scholar]
  48. Goodall J, Mateo J, Yuan W, Mossop H, Porta N et al. 2017. Circulating cell-free DNA to guide prostate cancer treatment with PARP inhibition. Cancer Discov 7:91006–17
    [Google Scholar]
  49. Guillemette S, Serra RW, Peng M, Hayes JA, Konstantinopoulos PA et al. 2015. Resistance to therapy in BRCA2 mutant cells due to loss of the nucleosome remodeling factor CHD4. Genes Dev 29:5489–94
    [Google Scholar]
  50. Gupta R, Somyajit K, Narita T, Maskey E, Stanlie A et al. 2018. DNA repair network analysis reveals shieldin as a key regulator of NHEJ and PARP inhibitor sensitivity. Cell 173:4972–88
    [Google Scholar]
  51. Helleday T. 2011. The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings. Mol. Oncol. 5:4387–93
    [Google Scholar]
  52. Hottiger MO, Hassa PO, Lüscher B, Schüler H, Koch-Nolte F 2010. Toward a unified nomenclature for mammalian ADP-ribosyltransferases. Trends Biochem. Sci. 35:4208–19
    [Google Scholar]
  53. Iorio F, Knijnenburg TA, Vis DJ, Bignell GR, Menden MP et al. 2016. A landscape of pharmacogenomic interactions in cancer. Cell 166:3740–54
    [Google Scholar]
  54. Jackson SP, Bartek J 2009. The DNA-damage response in human biology and disease. Nature 461:72671071–78
    [Google Scholar]
  55. Jaspers JE, Kersbergen A, Boon U, Sol W, van Deemter L et al. 2013. Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors. Cancer Discov 3:168–81
    [Google Scholar]
  56. Jiang J, Lu Y, Li Z, Li L, Niu D et al. 2017. Ganetespib overcomes resistance to PARP inhibitors in breast cancer by targeting core proteins in the DNA repair machinery. Investig. New Drugs. 35:3251–251
    [Google Scholar]
  57. Johnson N, Johnson SF, Yao W, Li Y-C, Choi Y-E et al. 2013. Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance. PNAS 110:4217041–46
    [Google Scholar]
  58. Johnson N, Li Y-C, Walton ZE, Cheng KA, Li D et al. 2011. Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition. Nat. Med. 17:7875–82
    [Google Scholar]
  59. Johnson SF, Cruz C, Greifenberg AK, Dust S, Stover DG et al. 2016. CDK12 inhibition reverses de novo and acquired PARP inhibitor resistance in BRCA wild-type and mutated models of triple-negative breast cancer. Cell Rep 17:92367–81
    [Google Scholar]
  60. Joshi PM, Sutor SL, Huntoon CJ, Karnitz LM 2014. Ovarian cancer-associated mutations disable catalytic activity of CDK12, a kinase that promotes homologous recombination repair and resistance to cisplatin and poly(ADP-ribose) polymerase inhibitors. J. Biol. Chem. 289:139247–53
    [Google Scholar]
  61. Kim MY, Zhang T, Kraus WL 2005. Poly(ADP-ribosyl)ation by PARP-1: ‘PAR-laying’ NAD+ into a nuclear signal. Genes Dev 19:171951–67
    [Google Scholar]
  62. Kolinjivadi AM, Sannino V, De Antoni A, Zadorozhny K, Kilkenny M et al. 2017. Smarcal1-mediated fork reversal triggers Mre11-dependent degradation of nascent DNA in the absence of Brca2 and stable Rad51 nucleofilaments. Mol. Cell 67:5867–81.e7
    [Google Scholar]
  63. Kondrashova O, Nguyen M, Shield-Artin K, Tinker AV, Teng NNH et al. 2017. Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma. Cancer Discov 7:9984–98
    [Google Scholar]
  64. Konstantinopoulos PA, Wilson AJ, Saskowski J, Wass E, Khabele D 2014. Suberoylanilide hydroxamic acid (SAHA) enhances olaparib activity by targeting homologous recombination DNA repair in ovarian cancer. Gynecol. Oncol. 133:3599–606
    [Google Scholar]
  65. Krawczyk PM, Eppink B, Essers J, Stap J, Rodermond H et al. 2011. Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly (ADP-ribose) polymerase-1 inhibition. PNAS 108:249851–56
    [Google Scholar]
  66. Lazzerini-Denchi E, Sfeir A 2016. Stop pulling my strings—what telomeres taught us about the DNA damage response. Nat. Rev. Mol. Cell Biol. 17:6364–78
    [Google Scholar]
  67. Lemaçon D, Jackson J, Quinet A, Brickner JR, Li S et al. 2017. MRE11 and EXO1 nucleases degrade reversed forks and elicit MUS81-dependent fork rescue in BRCA2-deficient cells. Nat. Commun. 8:1860
    [Google Scholar]
  68. Leung AKL. 2014. Poly(ADP-ribose): an organizer of cellular architecture. J. Cell Biol. 205:5613–19
    [Google Scholar]
  69. Lheureux S, Bruce JP, Burnier JV, Karakasis K, Shaw PA et al. 2017. Somatic BRCA1/2 recovery as a resistance mechanism after exceptional response to poly (ADP-ribose) polymerase inhibition. J. Clin. Oncol. 35:111240–49
    [Google Scholar]
  70. Lieber MR. 2010. The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu. Rev. Biochem. 79:181–211
    [Google Scholar]
  71. Liu C, Wu J, Paudyal SC, You Z, Yu X 2013. CHFR is important for the first wave of ubiquitination at DNA damage sites. Nucleic Acids Res 41:31698–710
    [Google Scholar]
  72. Lok BH, Gardner EE, Schneeberger VE, Ni A, Desmeules P et al. 2017. PARP inhibitor activity correlates with SLFN11 expression and demonstrates synergy with temozolomide in small cell lung cancer. Clin. Cancer Res. 23:2523–35
    [Google Scholar]
  73. Lord CJ, Ashworth A 2016. BRCAness revisited. Nat. Rev. Cancer 16:2110–20
    [Google Scholar]
  74. Lord CJ, Ashworth A 2017. PARP inhibitors: synthetic lethality in the clinic. Science 355:63301152–58
    [Google Scholar]
  75. Lupo B, Trusolino L 2014. Inhibition of poly(ADP-ribosyl)ation in cancer: old and new paradigms revisited. Biochim. Biophys. Acta 1846:1201–15
    [Google Scholar]
  76. Maréchal A, Zou L 2013. DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb. Perspect. Biol. 5:9a012716
    [Google Scholar]
  77. Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H et al. 2015. DNA-repair defects and olaparib in metastatic prostate cancer. N. Engl. J. Med. 373:181697–708
    [Google Scholar]
  78. Mateos-Gomez PA, Gong F, Nair N, Miller KM, Lazzerini-Denchi E, Sfeir A 2015. Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination. Nature 518:7538254–57
    [Google Scholar]
  79. Mayor P, Gay LM, Lele S, Elvin JA 2017. BRCA1 reversion mutation acquired after treatment identified by liquid biopsy. Gynecol. Oncol. Rep. 21:57–60
    [Google Scholar]
  80. Miao Z-H, Player A, Shankavaram U, Wang Y-H, Zimonjic DB et al. 2007. Nonclassic functions of human topoisomerase I: genome-wide and pharmacologic analyses. Cancer Res 67:188752–61
    [Google Scholar]
  81. Mijic S, Zellweger R, Chappidi N, Berti M, Jacobs K et al. 2017. Replication fork reversal triggers fork degradation in BRCA2-defective cells. Nat. Commun. 8:1859
    [Google Scholar]
  82. Min A, Im S-A, Kim DK, Song S-H, Kim H-J et al. 2015. Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), enhances anti-tumor effects of the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib in triple-negative breast cancer cells. Breast Cancer Res 17:33
    [Google Scholar]
  83. Moynahan ME, Jasin M 2010. Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat. Rev. Mol. Cell Biol. 11:3196–207
    [Google Scholar]
  84. Mu Y, Lou J, Srivastava M, Zhao B, Feng X et al. 2016. SLFN11 inhibits checkpoint maintenance and homologous recombination repair. EMBO Rep 17:194–109
    [Google Scholar]
  85. Murai J, Feng Y, Yu GK, Ru Y, Tang S-W et al. 2016. Resistance to PARP inhibitors by SLFN11 inactivation can be overcome by ATR inhibition. Oncotarget 7:4776534–50
    [Google Scholar]
  86. Murai J, Huang SY, Das BB, Renaud A, Zhang Y et al. 2012. Trapping of PARP1 and PARP2 by clinical PARP inhibitors. Cancer Res 72:215588–99
    [Google Scholar]
  87. Murai J, Huang SY, Renaud A, Zhang Y, Ji J et al. 2014.a Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib. Mol. Cancer Ther. 13:2433–43
    [Google Scholar]
  88. Murai J, Tang S-W, Leo E, Baechler SA, Redon CE et al. 2018. SLFN11 blocks stressed replication forks independently of ATR. Mol. Cell 69:3371–384.e6
    [Google Scholar]
  89. Murai J, Zhang Y, Morris J, Ji J, Takeda S et al. 2014.b Rationale for poly(ADP-ribose) polymerase (PARP) inhibitors in combination therapy with camptothecins or temozolomide based on PARP trapping versus catalytic inhibition. J. Pharmacol. Exp. Ther. 349:3408–16
    [Google Scholar]
  90. Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D et al. 2016. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature 534:760547–54
    [Google Scholar]
  91. Noordermeer SM, Adam S, Setiaputra D, Barazas M, Pettitt SJ et al. 2018. The shieldin complex mediates 53BP1-dependent DNA repair. Nature 560:7716117–21
    [Google Scholar]
  92. Norquist B, Wurz KA, Pennil CC, Garcia R, Gross J et al. 2011. Secondary somatic mutations restoring BRCA1/2 predict chemotherapy resistance in hereditary ovarian carcinomas. J. Clin. Oncol. 29:223008–15
    [Google Scholar]
  93. O'Connor MJ. 2015. Targeting the DNA damage response in cancer. Mol. Cell 60:4547–60
    [Google Scholar]
  94. Ohmoto A, Yachida S 2017. Current status of poly(ADP-ribose) polymerase inhibitors and future directions. OncoTargets Ther 10:5195–208
    [Google Scholar]
  95. Oplustil O'Connor L, Rulten SL, Cranston AN, Odedra R, Brown H et al. 2016. The PARP inhibitor AZD2461 provides insights into the role of PARP3 inhibition for both synthetic lethality and tolerability with chemotherapy in preclinical models. Cancer Res 76:206084–94
    [Google Scholar]
  96. Pascal JM, Ellenberger T 2015. The rise and fall of poly(ADP-ribose): an enzymatic perspective. DNA Repair 32:10–16
    [Google Scholar]
  97. Patch A-M, Christie EL, Etemadmoghadam D, Garsed DW, George J et al. 2015. Whole-genome characterization of chemoresistant ovarian cancer. Nature 521:7553489–94
    [Google Scholar]
  98. Pettitt SJ, Krastev DB, Brandsma I, Dréan A, Song F et al. 2018. Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance. Nat Commun 9:1849
    [Google Scholar]
  99. Pettitt SJ, Rehman FL, Bajrami I, Brough R, Wallberg F et al. 2013. A genetic screen using the PiggyBac transposon in haploid cells identifies Parp1 as a mediator of olaparib toxicity. PLOS ONE 8:4e61520
    [Google Scholar]
  100. Pishvaian MJ, Biankin AV, Bailey P, Chang DK, Laheru D et al. 2017. BRCA2 secondary mutation-mediated resistance to platinum and PARP inhibitor-based therapy in pancreatic cancer. Br. J. Cancer 116:81021–26
    [Google Scholar]
  101. Pommier Y, O'Connor MJ, de Bono J 2016. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action. Sci. Transl. Med. 8:362362ps17
    [Google Scholar]
  102. Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W et al. 2016. Inherited DNA-repair gene mutations in men with metastatic prostate cancer. N. Engl. J. Med. 375:5443–53
    [Google Scholar]
  103. Quigley D, Alumkal JJ, Wyatt AW, Kothari V, Foye A et al. 2017. Analysis of circulating cell-free DNA identifies multiclonal heterogeneity of BRCA2 reversion mutations associated with resistance to PARP inhibitors. Cancer Discov 7:9999–1005
    [Google Scholar]
  104. Ray Chaudhuri A, Callen E, Ding X, Gogola E, Duarte AA et al. 2016. Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature 535:7612382–87
    [Google Scholar]
  105. Ray Chaudhuri A, Hashimoto Y, Herrador R, Neelsen KJ, Fachinetti D et al. 2012. Topoisomerase I poisoning results in PARP-mediated replication fork reversal. Nat. Struct. Mol. Biol. 19:4417–23
    [Google Scholar]
  106. Ray Chaudhuri A, Nussenzweig A 2017. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat. Rev. Mol. Cell Biol. 18:10610–21
    [Google Scholar]
  107. Robinson D, Van Allen EM, Wu Y-M, Schultz N, Lonigro RJ et al. 2015. Integrative clinical genomics of advanced prostate cancer. Cell 162:2454
    [Google Scholar]
  108. Rondinelli B, Gogola E, Yücel H, Duarte AA, van de Ven M et al. 2017. EZH2 promotes degradation of stalled replication forks by recruiting MUS81 through histone H3 trimethylation. Nat. Cell Biol. 19:111371–78
    [Google Scholar]
  109. Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AOH et al. 2008. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. PNAS 105:4417079–84
    [Google Scholar]
  110. Roy R, Chun J, Powell SN 2011. BRCA1 and BRCA2: different roles in a common pathway of genome protection. Nat. Rev. Cancer 12:168–78
    [Google Scholar]
  111. Sakai W, Swisher EM, Jacquemont C, Chandramohan KV, Couch FJ et al. 2009. Functional restoration of BRCA2 protein by secondary BRCA2 mutations in BRCA2-mutated ovarian carcinoma. Cancer Res 69:166381–86
    [Google Scholar]
  112. Sakai W, Swisher EM, Karlan BY, Agarwal MK, Higgins J et al. 2008. Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature 451:71821116–20
    [Google Scholar]
  113. Schlacher K, Christ N, Siaud N, Egashira A, Wu H, Jasin M 2011. Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11. Cell 145:4529–42
    [Google Scholar]
  114. Schlacher K, Wu H, Jasin M 2012. A distinct replication fork protection pathway connects Fanconi anemia tumor suppressors to RAD51-BRCA1/2. Cancer Cell 22:1106–16
    [Google Scholar]
  115. Scully R. 2000. Role of BRCA gene dysfunction in breast and ovarian cancer predisposition. Breast Cancer Res 2:5324–30
    [Google Scholar]
  116. Shibata A. 2017. Regulation of repair pathway choice at two-ended DNA double-strand breaks. Mutat. Res. 803–805:51–55
    [Google Scholar]
  117. Sidorova J. 2017. A game of substrates: replication fork remodeling and its roles in genome stability and chemo-resistance. Cell Stress 1:3115–33
    [Google Scholar]
  118. Stewart CA, Tong P, Cardnell RJ, Sen T, Li L et al. 2017. Dynamic variations in epithelial-to-mesenchymal transition (EMT), ATM, and SLFN11 govern response to PARP inhibitors and cisplatin in small cell lung cancer. Oncotarget 8:1728575–87
    [Google Scholar]
  119. Swisher EM, Sakai W, Karlan BY, Wurz K, Urban N, Taniguchi T 2008. Secondary BRCA1 mutations in BRCA1-mutated ovarian carcinomas with platinum resistance. Cancer Res 68:82581–86
    [Google Scholar]
  120. Taglialatela A, Alvarez S, Leuzzi G, Sannino V, Ranjha L et al. 2017. Restoration of replication fork stability in BRCA1- and BRCA2-deficient cells by inactivation of SNF2-family fork remodelers. Mol. Cell 68:2414–30.e8
    [Google Scholar]
  121. Ter Brugge P, Kristel P, van der Burg E, Boon U, de Maaker M et al. 2016. Mechanisms of therapy resistance in patient-derived xenograft models of BRCA1-deficient breast cancer. J. Natl. Cancer Inst. 108:11djw148
    [Google Scholar]
  122. Tkáč J, Xu G, Adhikary H, Young JTF, Gallo D et al. 2016. HELB is a feedback inhibitor of DNA end resection. Mol. Cell 61:3405–18
    [Google Scholar]
  123. Turner N, Tutt A, Ashworth A 2004. Hallmarks of “BRCAness” in sporadic cancers. Nat. Rev. Cancer. 4:10814–19
    [Google Scholar]
  124. Vujanovic M, Krietsch J, Raso MC, Terraneo N, Zellweger R et al. 2017. Replication fork slowing and reversal upon DNA damage require PCNA polyubiquitination and ZRANB3 DNA translocase activity. Mol. Cell 67:5882–90.e5
    [Google Scholar]
  125. Waddell N, Pajic M, Patch A-M, Chang DK, Kassahn KS et al. 2015. Whole genomes redefine the mutational landscape of pancreatic cancer. Nature 518:7540495–501
    [Google Scholar]
  126. Wang J, Aroumougame A, Lobrich M, Li Y, Chen D et al. 2014. PTIP associates with Artemis to dictate DNA repair pathway choice. Genes Dev 28:242693–98
    [Google Scholar]
  127. Ward IM, Minn K, van Deursen J, Chen J 2003. p53 binding protein 53BP1 is required for DNA damage responses and tumor suppression in mice. Mol. Cell Biol. 23:72556–63
    [Google Scholar]
  128. Weigelt B, Comino-Méndez I, de Bruijn I, Tian L, Meisel JL et al. 2017. Diverse BRCA1 and BRCA2 reversion mutations in circulating cell-free DNA of therapy-resistant breast or ovarian cancer. Clin. Cancer Res. 23:216708–20
    [Google Scholar]
  129. Wu C-P, Calcagno AM, Ambudkar SV 2008. Reversal of ABC drug transporter-mediated multidrug resistance in cancer cells: evaluation of current strategies. Curr. Mol. Pharmacol. 1:293–105
    [Google Scholar]
  130. Xu G, Chapman JR, Brandsma I, Yuan J, Mistrik M et al. 2015. REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature 521:7553541–44
    [Google Scholar]
  131. Yazinski SA, Comaills V, Buisson R, Genois M-M, Nguyen HD et al. 2017. ATR inhibition disrupts rewired homologous recombination and fork protection pathways in PARP inhibitor-resistant BRCA-deficient cancer cells. Genes Dev 31:3318–32
    [Google Scholar]
  132. Ying S, Hamdy FC, Helleday T 2012. Mre11-dependent degradation of stalled DNA replication forks is prevented by BRCA2 and PARP1. Cancer Res 72:112814–21
    [Google Scholar]
  133. Zimmermann M, Lottersberger F, Buonomo SB, Sfeir A, de Lange T 2013. 53BP1 regulates DSB repair using Rif1 to control 5′ end resection. Science 339:6120700–4
    [Google Scholar]
  134. Zoppoli G, Regairaz M, Leo E, Reinhold WC, Varma S et al. 2012. Putative DNA/RNA helicase Schlafen-11 (SLFN11) sensitizes cancer cells to DNA-damaging agents. PNAS 109:3715030–35
    [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-030617-050232
Loading
/content/journals/10.1146/annurev-cancerbio-030617-050232
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error