Seminars in Radiation Oncology
Volume 20, Issue 4 , Pages 274-281 , October 2010

Poly(ADP-Ribose) Polymerase Inhibition as a Model for Synthetic Lethality in Developing Radiation Oncology Targets

  • Anthony J. Chalmers, MD, PhD, FRCR

      Affiliations

    • Genome Damage and Stability Centre, University of Sussex, Brighton, United Kingdom
    • Corresponding Author InformationAddress reprint requests to Anthony J. Chalmers, MD, PhD, FRCR, Brighton and Sussex Medical School and Genome Damage and Stability Centre, University of Sussex, Falmer BN1 9RQ, UK
    • ,
  • Mina Lakshman, PhD

      Affiliations

    • Departments of Radiation Oncology and Medical Biophysics, University of Toronto and Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada
    • ,
  • Norman Chan, BSc

      Affiliations

    • Departments of Radiation Oncology and Medical Biophysics, University of Toronto and Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada
    • ,
  • Robert G. Bristow, MD, PhD, FRCPC

      Affiliations

    • Departments of Radiation Oncology and Medical Biophysics, University of Toronto and Ontario Cancer Institute/Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada

References 

  1. D'Amours D, Desnoyers S, D'Silva I, et al. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J. 1999;342:249–268
  2. Ame JC, Spenlehauer C, de Murcia G. The PARP superfamily. Bioessays. 2004;26:882–893
  3. Woon EC, Threadgill MD. Poly(ADP-ribose)polymerase inhibition—Where now?. Curr Med Chem. 2005;12:2373–2392
  4. Chalmers AJ. The potential role and application of PARP inhibitors in cancer treatment. Br Med Bull. 2009;89:23–40
  5. Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005;434:913–917
  6. Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005;434:917–921
  7. Petermann E, Keil C, Oei SL. Importance of poly(ADP-ribose) polymerases in the regulation of DNA-dependent processes. Cell Mol Life Sci. 2005;62:731–738
  8. O'Driscoll M, Jeggo PA. The role of double-strand break repair—Insights from human genetics. Nat Rev Genet. 2006;7:45–54
  9. Caldecott KW. Protein-protein interactions during mammalian DNA single-strand break repair. Biochem Soc Trans. 2003;31:247–251
  10. Dantzer F, de la Rubia G, Menissier-De Murcia J, et al. Base excision repair is impaired in mammalian cells lacking poly(ADP-ribose) polymerase-1. Biochemistry. 2000;39:7559–7569
  11. Horton JK, Wilson SH. Hypersensitivity phenotypes associated with genetic and synthetic inhibitor-induced base excision repair deficiency. DNA Repair (Amst). 2007;6:530–543
  12. Noel G, Godon C, Fernet M, et al. Radiosensitization by the poly(ADP-ribose) polymerase inhibitor 4-amino-1,8-naphthalimide is specific of the S phase of the cell cycle and involves arrest of DNA synthesis. Mol Cancer Ther. 2006;5:564–574
  13. Dungey FA, Loser DA. Chalmers: replication-dependent radiosensitization of human glioma cells by inhibition of poly(ADP-ribose) polymerase: Mechanisms and therapeutic potential. AJM Int J Radiat Oncol Biol Phys. 2008;72:1188–1197
  14. Godon C, Cordelieres FP, Biard D, et al. PARP inhibition versus PARP-1 silencing: different outcomes in terms of single-strand break repair and radiation susceptibility. Nucleic Acids Res. 2008;36:4454–4464
  15. Kastan MB, Bartek J. Cell-cycle checkpoints and cancer. Nature. 2004;432:316–323
  16. Schlicker A, Peschke P, Burkle A, et al. Four-amino-1,8-naphthalimide: A novel inhibitor of poly(ADP-ribose) polymerase and radiation sensitizer. Int J Radiat Biol. 1999;75:91–100
  17. Russo AL, Kwon HC, Burgan WE, et al. In vitro and in vivo radiosensitization of glioblastoma cells by the poly (ADP-ribose) polymerase inhibitor E7016. Clin Cancer Res. 2009;15:607–612
  18. Donawho CK, Luo Y, Penning TD, et al. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res. 2007;13:2728–2737
  19. Noel G, Giocanti N, Fernet M, et al. Poly(ADP-ribose) polymerase (PARP-1) is not involved in DNA double-strand break recovery. BMC Cell Biol. 2003;4:7
  20. Schultz N, Lopez E, Saleh-Gohari N, et al. Poly(ADP-ribose) polymerase (PARP-1) has a controlling role in homologous recombination. Nucleic Acids Res. 2003;31:4959–4964
  21. Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009;361:123–134
  22. Gupta A, Yang Q, Pandita RK, et al. Cell cycle checkpoint defects contribute to genomic instability in PTEN deficient cells independent of DNA DSB repair. Cell Cycle. 2009;8:2198–2210
  23. Mendes-Pereira AM, Martin SA, Brough R, et al. Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors (EMBO). Mol Med. 2009;1:315–322
  24. Fan R, Kumaravel TS, Jalali F, et al. Defective DNA strand break repair after DNA damage in prostate cancer cells: implications for genetic instability and prostate cancer progression. Cancer Res. 2004;64:8526–8533
  25. Ishkanian AS, Mallof CA, Ho J, et al. High-resolution array CGH identifies novel regions of genomic alteration in intermediate-risk prostate cancer. Prostate. 2009;69:1091–1100
  26. Bristow RG, Ozcelik H, Jalali F, et al. Homologous recombination and prostate cancer: A model for novel DNA repair targets and therapies. Radiother Oncol. 2007;83:220–230
  27. Dungey FA, Caldecott KW, Chalmers AJ. Enhanced radiosensitization of human glioma cells by combining inhibition of poly(ADP-ribose) polymerase with inhibition of heat shock protein 90. Mol Cancer Ther. 2009;8:2243–2254
  28. Bennardo N, Cheng A, Huang N, et al. Alternative-NHEJ is a mechanistically distinct pathway of mammalian chromosome break repair. PLoS Genet. 2008;4:e1000110
  29. Wang M, Wu W, Rosidi B, et al. PARP-1 and ku compete for repair of DNA double strand breaks by distinct NHEJ pathways. Nucleic Acids Res. 2006;34:6170–6182
  30. Loser DA, Shibata A, Shibata AK, et al. Chalmers: Sensitization to radiation and alkylating agents by inhibitors of poly(ADP-ribose) polymerase is enhanced in cells deficient in DNA double-strand break repair. Mol Cancer Ther. 2010;9:1775–1787
  31. Martin SA, Lord CJ, Ashworth A. DNA repair deficiency as a therapeutic target in cancer. Curr Opin Genet Dev. 2008;18:80–86
  32. Bartkova J, Horejsi Z, Koed K, et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature. 2005;434:864–870
  33. Starcevic D, Dalal S, Sweasy JB. Is there a link between DNA polymerase beta and cancer?. Cell Cycle. 2004;3:998–1001
  34. Hu Z, Ma H, Chen F, et al. XRCC1 polymorphisms and cancer risk: A meta-analysis of 38 case-control studies. Cancer Epidemiol Biomarkers Prev. 2005;14:1810–1818
  35. Bryant HE, Helleday T. Inhibition of poly (ADP-ribose) polymerase activates ATM which is required for subsequent homologous recombination repair. Nucleic Acids Res. 2006;34:1685–1691
  36. Williamson CT, Muzik H, Turhan AG, et al. ATM deficiency sensitizes mantle cell lymphoma cells to poly(ADP-ribose) polymerase-1 inhibitors. Mol Cancer Ther. 2010;9:347–357
  37. Lu HR, Wang X, Wang Y. A stronger DNA damage-induced G2 checkpoint due to over-activated CHK1 in the absence of PARP-1. Cell Cycle. 2006;5:2364–2370
  38. Liu SK, Olive PL, Bristow RG. Biomarkers for DNA DSB inhibitors and radiotherapy clinical trials. Cancer Metastasis Rev. 2008;27:445–458
  39. Bhogal N, Jalali F, Bristow RG. Microscopic imaging of DNA repair foci in irradiated normal tissues. Int J Radiat Biol. 2009;85:732–746
  40. Bhogal N, Kaspler P, Jalali F, et al. Late residual gamma-H2AX foci in murine skin are dose responsive and predict radiosensitivity in vivo. Radiat Res. 2010;173:1–9
  41. Cheng CL, Johnson SP, Keir ST, et al. Poly(ADP-ribose) polymerase-1 inhibition reverses temozolomide resistance in a DNA mismatch repair-deficient malignant glioma xenograft. Mol Cancer Ther. 2005;4:1364–1368
  42. Jones P, Altamura S, Boueres J, et al. Discovery of 2-{4-[(3S)-piperidine-3-yl] phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem. 2009;52:7170–7185
  43. Mason KA, Valdecanas D, Hunter NR, et al. INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase, enhances tumor response to doxorubicin. Invest New Drugs. 2008;26:1–5
  44. Menear KA, Adcock C, Boulter R, et al. Four-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phth alazin-1-one: A novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem. 2008;51:6581–6591
  45. Albert JM, Cao C, Kim KW, et al. Inhibition of poly(ADP-ribose) polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models. Clin Cancer Res. 2007;13:3033–3042
  46. Calabrese CR, Almassy R, Barton S, et al. Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J Natl Cancer Inst. 2004;96:56–67
  47. Hay T, Matthews JR, Pietzka L, et al. Poly(ADP-ribose) polymerase-1 inhibitor treatment regresses autochthonous (Breast Cancer 2/p53-mutant mammary tumors in vivo and delays tumor relapse in combination with carboplatin). Cancer Res. 2009;69:3850–3855
  48. Khan K, Araki K, Wang D, et al. Head and neck cancer radiosensitization by the novel poly(ADP-ribose) polymerase inhibitor GPI-15427. Head Neck. 2010;381–391
  49. Ali M, Telfer BA, McCrudden C, et al. Vasoactivity of AG014699, a clinically active small molecule inhibitor of poly(ADP-ribose) polymerase: A contributory factor to chemopotentiation in vivo?. Clin Cancer Res. 2009;15:6106–6112
  50. Bindra RS, Schaffer PJ, Meng A, et al. Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol Cell Biol. 2004;24:8504–8518
  51. Bristow RG, Hill RP. Hypoxia and metabolism (Hypoxia, DNA repair and genetic instability). Nat Rev Cancer. 2008;8:180–192
  52. Chan N, Koritzinsky M, Zhao H, et al. Chronic hypoxia decreases synthesis of homologous recombination proteins to offset chemoresistance and radioresistance. Cancer Res. 2008;68:605–614
  53. Meng AX, Jalali F, Cuddihy A, et al. Hypoxia down-regulates DNA double strand break repair gene expression in prostate cancer cells. Radiother Oncol. 2005;76:168–176
  54. Liu SK, Coackley C, Krause M, et al. A novel poly(ADP-ribose) polymerase inhibitor, ABT-888, radiosensitizes malignant human cell lines under hypoxia. Radiother Oncol. 2008;88:258–268
  55. Choudhury A, Zhao H, Jalali F, et al. Targeting homologous recombination using imatinib results in enhanced tumor cell chemosensitivity and radiosensitivity. Mol Cancer Ther. 2009;8:203–213

 Supported by operating grants from the Medical Research Council to AJC and the Terry Fox Research Institute, the Ontario Institute for Cancer Research, and an infrastructure grant from the Canadian Foundation for Innovation grant to the STTARR Innovation Facility to RGB. ML is a CIHR-EIRR21t Post-Doctoral Fellow, and RGB is a Canadian Cancer Society Research scientist.

PII: S1053-4296(10)00043-3

doi: 10.1016/j.semradonc.2010.06.001

Seminars in Radiation Oncology
Volume 20, Issue 4 , Pages 274-281 , October 2010

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