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Translational Research in Breast Cancer pp 105–123Cite as

Studies on DNA Damage Repair and Precision Radiotherapy for Breast Cancer

Part of the Advances in Experimental Medicine and Biology book series (AEMB,volume 1026)

Abstract

Radiotherapy acts as an important component of breast cancer management, which significantly decreases local recurrence in patients treated with conservative surgery or with radical mastectomy. On the foundation of technological innovation of radiotherapy setting, precision radiotherapy of cancer has been widely applied in recent years. DNA damage and its repair mechanism are the vital factors which lead to the formation of tumor. Moreover, the status of DNA damage repair in cancer cells has been shown to influence patient response to the therapy, including radiotherapy. Some genes can affect the radiosensitivity of tumor cell by regulating the DNA damage repair pathway. This chapter will describe the potential application of DNA damage repair in precision radiotherapy of breast cancer.

Keywords

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References

  1. Tubbs A, Nussenzweig A (2017) Endogenous DNA damage as a source of genomic instability in cancer. Cell 168:644–656

    CrossRef  CAS  PubMed  Google Scholar 

  2. Lukas J, Lukas C, Bartek J (2011) More than just a focus: the chromatin response to DNA damage and its role in genome integrity maintenance. Nat Cell Biol 13:1161–1169

    CrossRef  CAS  PubMed  Google Scholar 

  3. Aboussekhra A, Biggerstaff M, Shivji MK, Vilpo JA, Moncollin V, Podust VN, Protic M, Hubscher U, Egly JM, Wood RD (1995) Mammalian DNA nucleotide excision repair reconstituted with purified protein components. Cell 80:859–868

    CrossRef  CAS  PubMed  Google Scholar 

  4. Bartkova J, Horejsi Z, Koed K, Kramer A, Tort F, Zieger K, Guldberg P, Sehested M, Nesland JM, Lukas C, Orntoft T, Lukas J, Bartek J (2005) DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434:864–870

    CrossRef  CAS  PubMed  Google Scholar 

  5. Jackson SP, Bartek J (2009) The DNA-damage response in human biology and disease. Nature 461:1071–1078

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wojciechowski F, Leumann CJ (2011) Alternative DNA base-pairs: from efforts to expand the genetic code to potential material applications. Chem Soc Rev 40:5669–5679

    CrossRef  CAS  PubMed  Google Scholar 

  7. Aparicio OM (2013) Location, location, location: It’s all in the timing for replication origins. Genes Dev 27:117–128

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  8. Gilbert DM (2010) Evaluating genome-scale approaches to eukaryotic DNA replication. Nat Rev Genet 11:673–684

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  9. MacAlpine DM, Almouzni G (2013) Chromatin and DNA replication. Cold Spring Harb Perspect Biol 5:a10207

    CrossRef  CAS  Google Scholar 

  10. Mechali M, Yoshida K, Coulombe P, Pasero P (2013) Genetic and epigenetic determinants of DNA replication origins, position and activation. Curr Opin Genet Dev 23:124–131

    CrossRef  CAS  PubMed  Google Scholar 

  11. Mechali M (2010) Eukaryotic DNA replication origins: many choices for appropriate answers. Nat Rev Mol Cell Biol 11:728–738

    CrossRef  CAS  PubMed  Google Scholar 

  12. Lagerwerf S, Vrouwe MG, Overmeer RM, Fousteri MI, Mullenders LH (2011) DNA damage response and transcription. DNA Repair (Amst) 10:743–750

    CrossRef  CAS  Google Scholar 

  13. Hubscher U, Maga G (2011) DNA replication and repair bypass machines. Curr Opin Chem Biol 15:627–635

    CrossRef  PubMed  CAS  Google Scholar 

  14. Larrea AA, Lujan SA, Nick MS, Mieczkowski PA, Resnick MA, Gordenin DA, Kunkel TA (2010) Genome-wide model for the normal eukaryotic DNA replication fork. Proc Natl Acad Sci U S A 107:17674–17679

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lehmann AR (2003) Replication of damaged DNA. Cell Cycle 2:300–302

    CrossRef  CAS  PubMed  Google Scholar 

  16. Malumbres M (2011) Physiological relevance of cell cycle kinases. Physiol Rev 91:973–1007

    CrossRef  CAS  PubMed  Google Scholar 

  17. Brady CA, Jiang D, Mello SS, Johnson TM, Jarvis LA, Kozak MM, Kenzelmann BD, Basak S, Park EJ, McLaughlin ME, Karnezis AN, Attardi LD (2011) Distinct p53 transcriptional programs dictate acute DNA-damage responses and tumor suppression. Cell 145:571–583

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  18. Fotouhi A, Cornella N, Ramezani M, Wojcik A, Haghdoost S (2015) Investigation of micronucleus induction in MTH1 knockdown cells exposed to UVA, UVB or UVC. Mutat Res Genet Toxicol Environ Mutagen 793:161–165

    CrossRef  CAS  PubMed  Google Scholar 

  19. Joo W, Xu G, Persky NS, Smogorzewska A, Rudge DG, Buzovetsky O, Elledge SJ, Pavletich NP (2011) Structure of the FANCI-FANCD2 complex: insights into the Fanconi anemia DNA repair pathway. Science 333:312–316

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sobol RW, Horton JK, Kuhn R, Gu H, Singhal RK, Prasad R, Rajewsky K, Wilson SH (1996) Requirement of mammalian DNA polymerase-beta in base-excision repair. Nature 379:183–186

    CrossRef  CAS  PubMed  Google Scholar 

  21. Chiolo I, Minoda A, Colmenares SU, Polyzos A, Costes SV, Karpen GH (2011) Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair. Cell 144:732–744

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  22. Staszewski O, Baker RE, Ucher AJ, Martier R, Stavnezer J, Guikema JE (2011) Activation-induced cytidine deaminase induces reproducible DNA breaks at many non-Ig loci in activated B cells. Mol Cell 41:232–242

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhang J, Powell SN (2005) The role of the BRCA1 tumor suppressor in DNA double-strand break repair. Mol Cancer Res 3:531–539

    CrossRef  CAS  PubMed  Google Scholar 

  24. Ali R, Rakha EA, Madhusudan S, Bryant HE (2017) DNA damage repair in breast cancer and its therapeutic implications. Pathology 49:156–165

    CrossRef  CAS  PubMed  Google Scholar 

  25. Lord CJ, Ashworth A (2012) The DNA damage response and cancer therapy. Nature 481:287–294

    CrossRef  CAS  PubMed  Google Scholar 

  26. Deem A, Keszthelyi A, Blackgrove T, Vayl A, Coffey B, Mathur R, Chabes A, Malkova A (2011) Break-induced replication is highly inaccurate. PLoS Biol 9:e1000594

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  27. Rai R, Peng G, Li K, Lin SY (2007) DNA damage response: the players, the network and the role in tumor suppression. Cancer Genomics Proteomics 4:99–106

    CAS  PubMed  Google Scholar 

  28. Abraham RT (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev 15:2177–2196

    CrossRef  CAS  PubMed  Google Scholar 

  29. Helmink BA, Tubbs AT, Dorsett Y, Bednarski JJ, Walker LM, Feng Z, Sharma GG, McKinnon PJ, Zhang J, Bassing CH, Sleckman BP (2011) H2AX prevents CtIP-mediated DNA end resection and aberrant repair in G1-phase lymphocytes. Nature 469:245–249

    CrossRef  CAS  PubMed  Google Scholar 

  30. Lee JH, Choy ML, Ngo L, Venta-Perez G, Marks PA (2011) Role of checkpoint kinase 1 (Chk1) in the mechanisms of resistance to histone deacetylase inhibitors. Proc Natl Acad Sci U S A 108:19629–19634

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mills KD, Ferguson DO, Alt FW (2003) The role of DNA breaks in genomic instability and tumorigenesis. Immunol Rev 194:77–95

    CrossRef  CAS  PubMed  Google Scholar 

  32. Hurley PJ, Bunz F (2007) ATM and ATR: components of an integrated circuit. Cell Cycle 6:414–417

    CrossRef  CAS  PubMed  Google Scholar 

  33. Coutts AS, La Thangue N (2006) The p53 response during DNA damage: impact of transcriptional cofactors. Biochem Soc Symp 73:181–189

    CrossRef  CAS  Google Scholar 

  34. Takata M, Sasaki MS, Sonoda E, Morrison C, Hashimoto M, Utsumi H, Yamaguchi-Iwai Y, Shinohara A, Takeda S (1998) Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J 17:5497–5508

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  35. Rothkamm K, Krüger I, Thompson LH, Löbrich M (2003) Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol 23:5706–5715

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sjögren C, Ström L (2010) S-phase and DNA damage activated establishment of sister chromatid cohesion—importance for DNA repair. Exp Cell Res 316:1445–1453

    CrossRef  PubMed  CAS  Google Scholar 

  37. Bauerschmidt C, Arrichiello C, Burdak-Rothkamm S, Woodcock M, Hill MA, Stevens DL, Rothkamm K (2010) Cohesin promotes the repair of ionizing radiation-induced DNA double-strand breaks in replicated chromatin. Nucleic Acids Res 38:477–487

    CrossRef  CAS  PubMed  Google Scholar 

  38. Kuzminov A (2001) Single-strand interruptions in replicating chromosomes cause double-strand breaks. Proc Natl Acad Sci U S A 98:8241–8246

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  39. Caldecott KW (2001) Mammalian DNA single-strand break repair: an X-ra(y)ted affair. Bioessays 23:447–455

    CrossRef  CAS  PubMed  Google Scholar 

  40. Khoronenkova SV, Dianov GL (2015) ATM prevents DSB formation by coordinating SSB repair and cell cycle progression. Proc Natl Acad Sci U S A 112:3997–4002

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  41. Caldecott KW (2014) DNA single-strand break repair. Exp Cell Res 329:2–8

    CrossRef  CAS  PubMed  Google Scholar 

  42. Caldecott KW (2014) Protein ADP-ribosylation and the cellular response to DNA strand breaks. DNA Repair 19:108–113

    CrossRef  CAS  PubMed  Google Scholar 

  43. Darby S, McGale P, Correa C, Taylor C, Arriagada R, Clarke M, Cutter D, Davies C, Ewertz M, Godwin J, Gray R, Pierce L, Whelan T, Wang Y, Peto R (2011) Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 378:1707–1716

    CrossRef  CAS  PubMed  Google Scholar 

  44. Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y (2005) Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet 366:2087–2106

    CrossRef  CAS  PubMed  Google Scholar 

  45. (2000) Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials. Early breast cancer Trialists’ collaborative group. Lancet 355:1757–1770

    Google Scholar 

  46. Thariat J, Hannoun-Levi JM, Sun MA, Vuong T, Gerard JP (2013) Past, present, and future of radiotherapy for the benefit of patients. Nat Rev Clin Oncol 10:52–60

    CrossRef  CAS  PubMed  Google Scholar 

  47. Graham P (2014) Cardiac dosimetry for adjuvant left-sided breast radiotherapy: patterns with 2D- versus 3D-era planning and correlates of coronary dose with maximum depth of myocardial exposure. J Med Imaging Radiat Oncol 58:517–522

    PubMed  Google Scholar 

  48. Sugano Y, Mizuta M, Takao S, Shirato H, Sutherland KL, Date H (2015) Optimization of the fractionated irradiation scheme considering physical doses to tumor and organ at risk based on dose-volume histograms. Med Phys 42:6203–6210

    CrossRef  PubMed  Google Scholar 

  49. Jackson A, Marks LB, Bentzen SM, Eisbruch A, Yorke ED, Ten HR, Constine LS, Deasy JO (2010) The lessons of QUANTEC: recommendations for reporting and gathering data on dose-volume dependencies of treatment outcome. Int J Radiat Oncol Biol Phys 76:S155–S160

    CrossRef  PubMed  PubMed Central  Google Scholar 

  50. Nagai A, Shibamoto Y, Yoshida M, Inoda K, Kikuchi Y (2017) Intensity-modulated radiotherapy using two static ports of tomotherapy for breast cancer after conservative surgery: Dosimetric comparison with other treatment methods and 3-year clinical results. J Radiat Res:1–8

    Google Scholar 

  51. Botteri E, Bagnardi V, Rotmensz N, Gentilini O, Disalvatore D, Bazolli B, Luini A, Veronesi U (2010) Analysis of local and regional recurrences in breast cancer after conservative surgery. Ann Oncol 21:723–728

    CrossRef  CAS  PubMed  Google Scholar 

  52. Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, Aguilar M, Marubini E (2002) Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347:1227–1232

    CrossRef  PubMed  Google Scholar 

  53. Whelan TJ, Olivotto IA, Parulekar WR, Ackerman I, Chua BH, Nabid A, Vallis KA, White JR, Rousseau P, Fortin A, Pierce LJ, Manchul L, Chafe S, Nolan MC, Craighead P, Bowen J, McCready DR, Pritchard KI, Gelmon K, Murray Y, Chapman JA, Chen BE, Levine MN (2015) Regional nodal irradiation in early-stage breast cancer. N Engl J Med 373:307–316

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  54. Orlandi E, Palazzi M, Pignoli E, Fallai C, Giostra A, Olmi P (2010) Radiobiological basis and clinical results of the simultaneous integrated boost (SIB) in intensity modulated radiotherapy (IMRT) for head and neck cancer: a review. Crit Rev Oncol Hematol 73:111–125

    CrossRef  PubMed  Google Scholar 

  55. Coles C, Agrawal R, Ah-See ML, Algurafi H, Alhasso A, Brunt AM, Chan C, Griffin C, Harnett A, Hopwood P (2016) Partial breast radiotherapy for women with early breast cancer: first results of local recurrence data for IMPORT LOW (CRUK/06/003). Eur J Cancer 57:S4

    Google Scholar 

  56. Donovan EM, Ciurlionis L, Fairfoul J, James H, Mayles H, Manktelow S, Raj S, Tsang Y, Tywman N, Yarnold J, Coles C (2011) Planning with intensity-modulated radiotherapy and tomotherapy to modulate dose across breast to reflect recurrence risk (IMPORT high trial). Int J Radiat Oncol Biol Phys 79:1064–1072

    CrossRef  PubMed  Google Scholar 

  57. Rusthoven KE, Kavanagh BD, Burri SH, Chen C, Cardenes H, Chidel MA, Pugh TJ, Kane M, Gaspar LE, Schefter TE (2009) Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. J Clin Oncol 27:1579–1584

    CrossRef  PubMed  Google Scholar 

  58. Rusthoven KE, Kavanagh BD, Cardenes H, Stieber VW, Burri SH, Feigenberg SJ, Chidel MA, Pugh TJ, Franklin W, Kane M, Gaspar LE, Schefter TE (2009) Multi-institutional phase I/II trial of stereotactic body radiation therapy for liver metastases. J Clin Oncol 27:1572–1578

    CrossRef  PubMed  Google Scholar 

  59. Milano MT, Zhang H, Metcalfe SK, Muhs AG, Okunieff P (2009) Oligometastatic breast cancer treated with curative-intent stereotactic body radiation therapy. Breast Cancer Res Treat 115:601–608

    CrossRef  PubMed  Google Scholar 

  60. Scorsetti M, Franceschini D, De Rose F, Comito T, Villa E, Iftode C, Navarria P, D’Agostino GR, Masci G, Torrisi R, Testori A, Tinterri C, Santoro A (2016) Stereotactic body radiation therapy: a promising chance for oligometastatic breast cancer. Breast 26:11–17

    CrossRef  PubMed  Google Scholar 

  61. Sung S, Lee JH, Lee JH, Kim SH, Kwak YK, Lee SW, Jeon YW, Suh YJ (2016) Displacement of surgical clips during postoperative radiotherapy in breast cancer patients who received breast-conserving surgery. J Breast Cancer 19:417–422

    CrossRef  PubMed  PubMed Central  Google Scholar 

  62. Cho O, Chun M, Oh YT, Kim MH, Park HJ, Heo JS, Noh OK (2013) Can initial diagnostic PET-CT aid to localize tumor bed in breast cancer radiotherapy: feasibility study using deformable image registration. Radiat Oncol 8:163

    CrossRef  PubMed  PubMed Central  Google Scholar 

  63. Giezen M, Kouwenhoven E, Scholten AN, Coerkamp EG, Heijenbrok M, Jansen WP, Mast ME, Petoukhova AL, Struikmans H (2011) Magnetic resonance imaging- versus computed tomography-based target volume delineation of the glandular breast tissue (clinical target volume breast) in breast-conserving therapy: an exploratory study. Int J Radiat Oncol Biol Phys 81:804–811

    CrossRef  PubMed  Google Scholar 

  64. Conroy L, Yeung R, Watt E, Quirk S, Long K, Hudson A, Phan T, Smith WL (2016) Evaluation of target and cardiac position during visually monitored deep inspiration breath-hold for breast radiotherapy. J Appl Clin Med Phys 17:25–36

    CrossRef  PubMed  Google Scholar 

  65. van Heijst TC, Philippens ME, Charaghvandi RK, den Hartogh MD, Lagendijk JJ, van den Bongard HJ, van Asselen B (2016) Quantification of intra-fraction motion in breast radiotherapy using supine magnetic resonance imaging. Phys Med Biol 61:1352–1370

    CrossRef  PubMed  CAS  Google Scholar 

  66. Lagendijk JJ, Raaymakers BW, Raaijmakers AJ, Overweg J, Brown KJ, Kerkhof EM, van der Put RW, Hardemark B, van Vulpen M, van der Heide UA (2008) MRI/linac integration. Radiother Oncol 86:25–29

    CrossRef  PubMed  Google Scholar 

  67. Calvo FA, Sole CV, Rivera S, Meirino R, Lizarraga S, Infante MA, Boldo E, Ferrer C, Marsiglia H, Deutsch E (2014) The use of radiotherapy for early breast cancer in woman at different ages. Clin Transl Oncol 16:680–685

    CrossRef  CAS  PubMed  Google Scholar 

  68. Marta GN, de Moraes FY (2015) Postoperative nodal irradiation in breast cancer patients with 1 to 3 axillary lymph nodes involved: The debate continues... Expert Rev Anticancer Ther 15:1257–1259

    Google Scholar 

  69. Speers C, Zhao S, Liu M, Bartelink H, Pierce LJ, Feng FY (2015) Development and validation of a novel radiosensitivity signature in human breast cancer. Clin Cancer Res 21:3667–3677

    CrossRef  CAS  PubMed  Google Scholar 

  70. Servant N, Bollet MA, Halfwerk H, Bleakley K, Kreike B, Jacob L, Sie D, Kerkhoven RM, Hupe P, Hadhri R, Fourquet A, Bartelink H, Barillot E, Sigal-Zafrani B, van de Vijver MJ (2012) Search for a gene expression signature of breast cancer local recurrence in young women. Clin Cancer Res 18:1704–1715

    CrossRef  CAS  PubMed  Google Scholar 

  71. van de Vijver MJ, He YD, Van’T VL, Dai H, Hart AA, Voskuil DW, Schreiber GJ, Peterse JL, Roberts C, Marton MJ, Parrish M, Atsma D, Witteveen A, Glas A, Delahaye L, van der Velde T, Bartelink H, Rodenhuis S, Rutgers ET, Friend SH, Bernards R (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999–2009

    CrossRef  PubMed  Google Scholar 

  72. Torres-Roca JF, Fulp WJ, Caudell JJ, Servant N, Bollet MA, van de Vijver M, Naghavi AO, Harris EE, Eschrich SA (2015) Integration of a radiosensitivity molecular signature into the assessment of local recurrence risk in breast cancer. Int J Radiat Oncol Biol Phys 93:631–638

    CrossRef  PubMed  Google Scholar 

  73. Kyndi M, Sorensen FB, Knudsen H, Overgaard M, Nielsen HM, Overgaard J (2008) Estrogen receptor, progesterone receptor, HER-2, and response to postmastectomy radiotherapy in high-risk breast cancer: the Danish breast cancer cooperative group. J Clin Oncol 26:1419–1426

    CrossRef  CAS  PubMed  Google Scholar 

  74. Tramm T, Kyndi M, Myhre S, Nord S, Alsner J, Sorensen FB, Sorlie T, Overgaard J (2014) Relationship between the prognostic and predictive value of the intrinsic subtypes and a validated gene profile predictive of loco-regional control and benefit from post-mastectomy radiotherapy in patients with high-risk breast cancer. Acta Oncol 53:1337–1346

    CrossRef  PubMed  Google Scholar 

  75. Bellon JR (2015) Personalized radiation oncology for breast cancer: the new frontier. J Clin Oncol 33:1998–2000

    CrossRef  PubMed  Google Scholar 

  76. Colleoni M, Rotmensz N, Peruzzotti G, Maisonneuve P, Viale G, Renne G, Casadio C, Veronesi P, Intra M, Torrisi R, Goldhirsch A (2004) Minimal and small size invasive breast cancer with no axillary lymph node involvement: the need for tailored adjuvant therapies. Ann Oncol 15:1633–1639

    CrossRef  CAS  PubMed  Google Scholar 

  77. Selz J, Stevens D, Jouanneau L, Labib A, Le Scodan R (2012) Prognostic value of molecular subtypes, ki67 expression and impact of postmastectomy radiation therapy in breast cancer patients with negative lymph nodes after mastectomy. Int J Radiat Oncol Biol Phys 84:1123–1132

    CrossRef  CAS  PubMed  Google Scholar 

  78. Zurrida S, Bagnardi V, Curigliano G, Mastropasqua MG, Orecchia R, Disalvatore D, Greco M, Cataliotti L, D’Aiuto G, Talakhadze N, Goldhirsch A, Viale G (2013) High Ki67 predicts unfavourable outcomes in early breast cancer patients with a clinically clear axilla who do not receive axillary dissection or axillary radiotherapy. Eur J Cancer 49:3083–3092

    CrossRef  CAS  PubMed  Google Scholar 

  79. Lowery AJ, Kell MR, Glynn RW, Kerin MJ, Sweeney KJ (2012) Locoregional recurrence after breast cancer surgery: a systematic review by receptor phenotype. Breast Cancer Res Treat 133:831–841

    CrossRef  PubMed  Google Scholar 

  80. Adamowicz K, Marczewska M, Jassem J (2009) Combining systemic therapies with radiation in breast cancer. Cancer Treat Rev 35:409–416

    CrossRef  PubMed  Google Scholar 

  81. Brollo J, Kneubil MC, Botteri E, Rotmensz N, Duso BA, Fumagalli L, Locatelli MA, Criscitiello C, Lohsiriwat V, Goldhirsch A, Leonardi MC, Orecchia R, Curigliano G (2013) Locoregional recurrence in patients with HER2 positive breast cancer. Breast 22:856–862

    CrossRef  PubMed  Google Scholar 

  82. Eiermann W, Bergh J, Cardoso F, Conte P, Crown J, Curtin NJ, Gligorov J, Gusterson B, Joensuu H, Linderholm BK, Martin M, Penault-Llorca F, Pestalozzi BC, Razis E, Sotiriou C, Tjulandin S, Viale G (2012) Triple negative breast cancer: proposals for a pragmatic definition and implications for patient management and trial design. Breast 21:20–26

    CrossRef  CAS  PubMed  Google Scholar 

  83. Moran MS (2015) Radiation therapy in the locoregional treatment of triple-negative breast cancer. Lancet Oncol 16:e113–e122

    CrossRef  PubMed  Google Scholar 

  84. Moser EC, Vrieling C (2012) Accelerated partial breast irradiation: the need for well-defined patient selection criteria, improved volume definitions, close follow-up and discussion of salvage treatment. Breast 21:707–715

    CrossRef  PubMed  Google Scholar 

  85. Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, Julian TB, Marks LB, Todor DA, Vicini FA, Whelan TJ, White J, Wo JY, Harris JR (2009) Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). J Am Coll Surg 209:269–277

    CrossRef  PubMed  Google Scholar 

  86. Polgar C, Van Limbergen E, Potter R, Kovacs G, Polo A, Lyczek J, Hildebrandt G, Niehoff P, Guinot JL, Guedea F, Johansson B, Ott OJ, Major T, Strnad V (2010) Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: recommendations of the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group based on clinical evidence (2009). Radiother Oncol 94:264–273

    CrossRef  PubMed  Google Scholar 

  87. Haffty BG, Hunt KK, Harris JR, Buchholz TA (2011) Positive sentinel nodes without axillary dissection: implications for the radiation oncologist. J Clin Oncol 29:4479–4481

    CrossRef  PubMed  Google Scholar 

  88. Kunkler IH, Canney P, van Tienhoven G, Russell NS (2008) Elucidating the role of chest wall irradiation in ‘intermediate-risk’ breast cancer: the MRC/EORTC SUPREMO trial. Clin Oncol (R Coll Radiol) 20:31–34

    CrossRef  CAS  Google Scholar 

  89. Lazzeroni M, Guerrieri-Gonzaga A, Botteri E, Leonardi MC, Rotmensz N, Serrano D, Varricchio C, Disalvatore D, Del CA, Bassi F, Pagani G, DeCensi A, Viale G, Bonanni B, Pruneri G (2013) Tailoring treatment for ductal intraepithelial neoplasia of the breast according to Ki-67 and molecular phenotype. Br J Cancer 108:1593–1601

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  90. Curigliano G, Disalvatore D, Esposito A, Pruneri G, Lazzeroni M, Guerrieri-Gonzaga A, Luini A, Orecchia R, Goldhirsch A, Rotmensz N, Bonanni B, Viale G (2015) Risk of subsequent in situ and invasive breast cancer in human epidermal growth factor receptor 2-positive ductal carcinoma in situ. Ann Oncol 26:682–687

    CrossRef  CAS  PubMed  Google Scholar 

  91. Solin LJ, Gray R, Baehner FL, Butler SM, Hughes LL, Yoshizawa C, Cherbavaz DB, Shak S, Page DL, Sledge GJ, Davidson NE, Ingle JN, Perez EA, Wood WC, Sparano JA, Badve S (2013) A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. J Natl Cancer Inst 105:701–710

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  92. Azria D, Gourgou S, Sozzi WJ, Zouhair A, Mirimanoff RO, Kramar A, Lemanski C, Dubois JB, Romieu G, Pelegrin A, Ozsahin M (2004) Concomitant use of tamoxifen with radiotherapy enhances subcutaneous breast fibrosis in hypersensitive patients. Br J Cancer 91:1251–1260

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  93. Azria D, Riou O, Castan F, Nguyen TD, Peignaux K, Lemanski C, Lagrange JL, Kirova Y, Lartigau E, Belkacemi Y, Bourgier C, Rivera S, Noel G, Clippe S, Mornex F, Hennequin C, Kramar A, Gourgou S, Pelegrin A, Fenoglietto P, Ozsahin EM (2015) Radiation-induced CD8 t-lymphocyte apoptosis as a predictor of breast fibrosis after radiotherapy: results of the prospective multicenter french trial. EBioMedicine 2:1965–1973

    CrossRef  PubMed  PubMed Central  Google Scholar 

  94. Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25:1329–1333

    CrossRef  PubMed  PubMed Central  Google Scholar 

  95. Wang B, Matsuoka S, Ballif BA, Zhang D, Smogorzewska A, Gygi SP, Elledge SJ (2007) Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. Science 316:1194–1198

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  96. Yun MH, Hiom K (2009) CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle. Nature 459:460–463

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  97. Chen L, Nievera CJ, Lee AY, Wu X (2008) Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA double-strand break repair. J Biol Chem 283:7713–7720

    CrossRef  CAS  PubMed  Google Scholar 

  98. Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R (1998) The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression. J Biol Chem 273:25388–25392

    CrossRef  CAS  PubMed  Google Scholar 

  99. Bunting SF, Callen E, Wong N, Chen HT, Polato F, Gunn A, Bothmer A, Feldhahn N, Fernandez-Capetillo O, Cao L, Xu X, Deng CX, Finkel T, Nussenzweig M, Stark JM, Nussenzweig A (2010) 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 141:243–254

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  100. Sharan SK, Morimatsu M, Albrecht U, Lim DS, Regel E, Dinh C, Sands A, Eichele G, Hasty P, Bradley A (1997) Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature 386:804–810

    CrossRef  CAS  PubMed  Google Scholar 

  101. Foray N, Randrianarison V, Marot D, Perricaudet M, Lenoir G, Feunteun J (1999) Gamma-rays-induced death of human cells carrying mutations of BRCA1 or BRCA2. Oncogene 18:7334–7342

    CrossRef  CAS  PubMed  Google Scholar 

  102. Scully R, Ganesan S, Vlasakova K, Chen J, Socolovsky M, Livingston DM (1999) Genetic analysis of BRCA1 function in a defined tumor cell line. Mol Cell 4:1093–1099

    CrossRef  CAS  PubMed  Google Scholar 

  103. Abbott DW, Thompson ME, Robinson-Benion C, Tomlinson G, Jensen RA, Holt JT (1999) BRCA1 expression restores radiation resistance in BRCA1-defective cancer cells through enhancement of transcription-coupled DNA repair. J Biol Chem 274:18808–18812

    CrossRef  CAS  PubMed  Google Scholar 

  104. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66–71

    CrossRef  CAS  PubMed  Google Scholar 

  105. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G (1995) Identification of the breast cancer susceptibility gene BRCA2. 378, pp 789–792

    Google Scholar 

  106. Rakha EA, Reis-Filho JS, Ellis IO (2008) Basal-like breast cancer: a critical review. J Clin Oncol 26:2568–2581

    CrossRef  PubMed  Google Scholar 

  107. Phillips KA, Andrulis IL, Goodwin PJ (1999) Breast carcinomas arising in carriers of mutations in BRCA1 or BRCA2: are they prognostically different? J Clin Oncol 17:3653–3663

    CrossRef  CAS  PubMed  Google Scholar 

  108. Boyd J, Sonoda Y, Federici MG, Bogomolniy F, Rhei E, Maresco DL, Saigo PE, Almadrones LA, Barakat RR, Brown CL, Chi DS, Curtin JP, Poynor EA, Hoskins WJ (2000) Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 283:2260–2265

    CrossRef  CAS  PubMed  Google Scholar 

  109. Hirai T, Shirai H, Fujimori H, Okayasu R, Sasai K, Masutani M (2012) Radiosensitization effect of poly(ADP-ribose) polymerase inhibition in cells exposed to low and high liner energy transfer radiation. Cancer Sci 103:1045–1050

    CrossRef  CAS  PubMed  Google Scholar 

  110. Zaremba T, Curtin NJ (2007) PARP inhibitor development for systemic cancer targeting. Anti Cancer Agents Med Chem 7:515–523

    CrossRef  CAS  Google Scholar 

  111. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O’Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS (2009) Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 361:123–134

    CrossRef  CAS  PubMed  Google Scholar 

  112. Fong PC, Yap TA, Boss DS, Carden CP, Mergui-Roelvink M, Gourley C, De Greve J, Lubinski J, Shanley S, Messiou C, A’Hern R, Tutt A, Ashworth A, Stone J, Carmichael J, Schellens JH, de Bono JS, Kaye SB (2010) Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J Clin Oncol 28:2512–2519

    CrossRef  CAS  PubMed  Google Scholar 

  113. Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M, Carmichael J (2010) Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 376:235–244

    CrossRef  CAS  PubMed  Google Scholar 

  114. Kaufman B (2015) SRSR, J B, G M, G F, SM S, a H, O R, M S, N L, K B, a F, SM D: Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 33:244–250

    CrossRef  CAS  PubMed  Google Scholar 

  115. Wilson RH, Evans TJ, Middleton MR, Molife LR, Spicer J, Dieras V, Roxburgh P, Giordano H, Jaw-Tsai S, Goble S, Plummer R (2017) A phase I study of intravenous and oral rucaparib in combination with chemotherapy in patients with advanced solid tumours. Br J Cancer 116:884–892

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  116. Castellano L, Giamas G, Jacob J, Coombes RC, Lucchesi W, Thiruchelvam P, Barton G, Jiao LR, Wait R, Waxman J, Hannon GJ, Stebbing J (2009) The estrogen receptor-alpha-induced microRNA signature regulates itself and its transcriptional response. Proc Natl Acad Sci U S A 106:15732–15737

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  117. Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor C, Wang YC, Dowsett M, Ingle J, Peto R (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378:771–784

    CrossRef  CAS  PubMed  Google Scholar 

  118. Chisamore MJ, Wilkinson HA, Flores O, Chen JD (2009) Estrogen-related receptor-alpha antagonist inhibits both estrogen receptor-positive and estrogen receptor-negative breast tumor growth in mouse xenografts. Mol Cancer Ther 8:672–681

    CrossRef  CAS  PubMed  Google Scholar 

  119. Liu YH, He N, Jiang SQ, Li X, Zhang JS (2011) Regulation of orphan receptor ERRα by estrogen and estrogen-related receptor antagonist in MCF-7 cell line. J Environ Health 28:677–680

    CAS  Google Scholar 

  120. Ciszewski WM, Tavecchio M, Dastych J, Curtin NJ (2014) DNA-PK inhibition by NU7441 sensitizes breast cancer cells to ionizing radiation and doxorubicin. Breast Cancer Res Treat 143:47–55

    CrossRef  CAS  PubMed  Google Scholar 

  121. Moll U, Lau R, Sypes MA, Gupta MM, Anderson CW (1999) DNA-PK, the DNA-activated protein kinase, is differentially expressed in normal and malignant human tissues. Oncogene 18:3114–3126

    CrossRef  CAS  PubMed  Google Scholar 

  122. Patel AG, Sarkaria JN, Kaufmann SH (2011) Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells. Proc Natl Acad Sci U S A 108(8):3406–11

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  123. Mansour WY, Rhein T, Dahm-Daphi J (2010) The alternative end-joining pathway for repair of DNA double-strand breaks requires PARP1 but is not dependent upon microhomologies. Nucleic Acids Res 38:6065–6077

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  124. Kim CH, Park SJ, Lee SH (2002) A targeted inhibition of DNA-dependent protein kinase sensitizes breast cancer cells following ionizing radiation. J Pharmacol Exp Ther 303:753–759

    CrossRef  CAS  PubMed  Google Scholar 

  125. Belenkov AI, Paiement JP, Panasci LC, Monia BP, Chow TY (2002) An antisense oligonucleotide targeted to human Ku86 messenger RNA sensitizes M059K malignant glioma cells to ionizing radiation, bleomycin, and etoposide but not DNA cross-linking agents. Cancer Res 62:5888–5896

    CAS  PubMed  Google Scholar 

  126. Bladen CL, Lam WK, Dynan WS, Kozlowski DJ (2005) DNA damage response and Ku80 function in the vertebrate embryo. Nucleic Acids Res 33:3002–3010

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  127. Sturgeon CM, Knight ZA, Shokat KM, Roberge M (2006) Effect of combined DNA repair inhibition and G2 checkpoint inhibition on cell cycle progression after DNA damage. Mol Cancer Ther 5:885–892

    CrossRef  CAS  PubMed  Google Scholar 

  128. Ayene IS, Ford LP, Koch CJ (2005) Ku protein targeting by Ku70 small interfering RNA enhances human cancer cell response to topoisomerase ii inhibitor and gamma radiation. Mol Cancer Ther 4:529–536

    CrossRef  CAS  PubMed  Google Scholar 

  129. Losada R, Rivero MT, Slijepcevic P, Goyanes V, Fernández JL (2005) Effect of Wortmannin on the repair profiles of DNA double-strand breaks in the whole genome and in interstitial telomeric sequences of Chinese hamster cells. Mutat Res 570:119–128

    CrossRef  CAS  PubMed  Google Scholar 

  130. Wilson DR, Simeonov A (2010) Small molecule inhibitors of DNA repair nuclease activities of APE1. Cell Mol Life Sci 67:3621–3631

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  131. Al-Safi RI, Odde S, Shabaik Y, Neamati N (2012) Small-molecule inhibitors of APE1 DNA repair function: an overview. Curr Mol Pharmacol 5:14–35

    CrossRef  CAS  PubMed  Google Scholar 

  132. Moore DH, Michael H, Tritt R, Parsons SH, Kelley MR (2000) Alterations in the expression of the DNA repair/redox enzyme APE/ref-1 in epithelial ovarian cancers. Clin Cancer Res 6:602–609

    CAS  PubMed  Google Scholar 

  133. Kelley MR, Cheng L, Foster R, Tritt R, Jiang J, Broshears J, Koch M (2001) Elevated and altered expression of the multifunctional DNA base excision repair and redox enzyme Ape1/ref-1 in prostate cancer. Clin Cancer Res 7:824–830

    CAS  PubMed  Google Scholar 

  134. Hadi MZ, Coleman MA, Fidelis K, Mohrenweiser HW, Wilson DR (2000) Functional characterization of Ape1 variants identified in the human population. Nucleic Acids Res 28:3871–3879

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  135. Kakolyris S, Kaklamanis L, Engels K, Turley H, Hickson ID, Gatter KC, Harris AL (1997) Human apurinic endonuclease 1 expression in a colorectal adenoma-carcinoma sequence. Cancer Res 57:1794–1797

    CAS  PubMed  Google Scholar 

  136. Abdel-Fatah TM, Perry C, Moseley P, Johnson K, Arora A, Chan S, Ellis IO, Madhusudan S (2014) Clinicopathological significance of human apurinic/apyrimidinic endonuclease 1 (APE1) expression in oestrogen-receptor-positive breast cancer. Breast Cancer Res Treat 143:411–421

    CrossRef  CAS  PubMed  Google Scholar 

  137. Poletto M, Di Loreto C, Marasco D, Poletto E, Puglisi F, Damante G, Tell G (2012) Acetylation on critical lysine residues of Apurinic/apyrimidinic endonuclease 1 (APE1) in triple negative breast cancers. Biochem Biophys Res Commun 424:34–39

    CrossRef  CAS  PubMed  Google Scholar 

  138. Sultana R, McNeill DR, Abbotts R, Mohammed MZ, Zdzienicka MZ, Qutob H, Seedhouse C, Laughton CA, Fischer PM, Patel PM, Wilson DM 3rd, Madhusudan S (2012) Synthetic lethal targeting of DNA double-strand break repair deficient cells by human apurinic/apyrimidinic endonuclease inhibitors. Int J Cancer 131:2433–2444

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  139. Wang D, Zhong ZY, Li MX, Xiang DB, Li ZP (2007) Vector-based APE1 small interfering RNA enhances the sensitivity of human osteosarcoma cells to endostatin in vivo. Cancer Sci 98:1993–2001

    CrossRef  CAS  PubMed  Google Scholar 

  140. Herring CJ, West CM, Wilks DP, Davidson SE, Hunter RD, Berry P, Forster G, MacKinnon J, Rafferty JA, Elder RH, Hendry JH, Margison GP (1998) Levels of the DNA repair enzyme human apurinic/apyrimidinic endonuclease(APE1, APEX, ref-1) are associated with the intrinsic radio-sensitivity of cervical cancers. Br J Cancer 78:1128–1133

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  141. Van Gent DC, Hoeijmakers JHJ, Kanaar R (2001) Chromosomal stability and the DNA double-strand break connection. Nat Rev Genet 2:196–206

    CrossRef  PubMed  Google Scholar 

  142. Marine JC, Lozano G (2010) Mdm2-mediated ubiquitylation: P53 and beyond. Cell Death Differ 17:93–102

    CrossRef  CAS  PubMed  Google Scholar 

  143. Khosravi R, Maya R, Gottlieb T, Oren M, Shiloh Y, Shkedy D (1999) Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in response to DNA damage. Proc Natl Acad Sci U S A 96:14973–14977

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  144. Errico A, Costanzo V (2012) Mechanisms of replication fork protection: a safeguard for genome stability. Crit Rev Biochem Mol Biol 47:222–235

    CrossRef  CAS  PubMed  Google Scholar 

  145. Mohni KN, Kavanaugh GM, Cortez D (2014) ATR pathway inhibition is synthetically lethal in cancer cells with ERCC1 deficiency. Cancer Res 74:2835–2845

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  146. Sultana R, Abdel-Fatah T, Abbotts R, Hawkes C, Albarakati N, Seedhouse C, Ball G, Chan S, Rakha EA, Ellis IO, Madhusudan S (2013) Targeting XRCC1 deficiency in breast cancer for personalized therapy. Cancer Res 73:1621–1634

    CrossRef  CAS  PubMed  Google Scholar 

  147. Shiloh Y (2003) ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer 3:155–168

    CrossRef  CAS  PubMed  Google Scholar 

  148. Biddlestone-Thorpe L, Sajjad M, Rosenberg E, Beckta JM, Valerie NC, Tokarz M, Adams BR, Wagner AF, Khalil A, Gilfor D, Golding SE, Deb S, Temesi DG, Lau A, O’Connor MJ, Choe KS, Parada LF, Lim SK, Mukhopadhyay ND, Valerie K (2013) ATM kinase inhibition preferentially sensitizes p53-mutant glioma to ionizing radiation. Clin Cancer Res 19:3189–3200

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  149. Yang H, Yoon SJ, Jin J, Choi SH, Seol HJ, Lee JI, Nam DH, Yoo HY (2011) Inhibition of checkpoint kinase 1 sensitizes lung cancer brain metastases to radiotherapy. Biochem Biophys Res Commun 406:53–58

    CrossRef  CAS  PubMed  Google Scholar 

  150. Borst GR, McLaughlin M, Kyula JN, Neijenhuis S, Khan A, Good J, Zaidi S, Powell NG, Meier P, Collins I, Garrett MD, Verheij M, Harrington KJ (2013) Targeted radiosensitization by the Chk1 inhibitor SAR-020106. Int J Radiat Oncol Biol Phys 85:1110–1118

    CrossRef  CAS  PubMed  Google Scholar 

  151. Peasland A, Wang LZ, Rowling E, Kyle S, Chen T, Hopkins A, Cliby WA, Sarkaria J, Beale G, Edmondson RJ, Curtin NJ (2011) Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines. Br J Cancer 105:372–381

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  152. Wickremsinhe ER, Hynes SM, Palmieri MD, Mitchell MI, Abraham TL, Rehmel JF, Chana E, Jost LM, Cassidy KC (2014) Disposition and metabolism of LY2603618, a Chk-1 inhibitor following intravenous administration in patients with advanced and/or metastatic solid tumors. Xenobiotica 44:827–841

    CrossRef  CAS  PubMed  Google Scholar 

  153. Shapiro GI, Tibes R, Gordon MS, Wong BY, Eder JP, Borad MJ, Mendelson DS, Vogelzang NJ, Bastos BR, Weiss GJ, Fernandez C, Sutherland W, Sato H, Pierceall WE, Weaver D, Slough S, Wasserman E, Kufe DW, Von Hoff D, Kawabe T, Sharma S (2011) Phase I studies of CBP501, a G2 checkpoint abrogator, as monotherapy and in combination with cisplatin in patients with advanced solid tumors. Clin Cancer Res 17:3431–3442

    CrossRef  CAS  PubMed  Google Scholar 

  154. Dees EC, Baker SD, O’Reilly S, Rudek MA, Davidson SB, Aylesworth C, Elza-Brown K, Carducci MA, Donehower RC (2005) A phase I and pharmacokinetic study of short infusions of UCN-01 in patients with refractory solid tumors. Clin Cancer Res 11:664–671

    CAS  PubMed  Google Scholar 

  155. Sausville EA, Arbuck SG, Messmann R, Headlee D, Bauer KS, Lush RM, Murgo A, Figg WD, Lahusen T, Jaken S, Jing X, Roberge M, Fuse E, Kuwabara T, Senderowicz AM (2001) Phase I trial of 72-hour continuous infusion UCN-01 in patients with refractory neoplasms. J Clin Oncol 19:2319–2333

    CrossRef  CAS  PubMed  Google Scholar 

  156. Sausville E, Lorusso P, Carducci M, Carter J, Quinn MF, Malburg L, Azad N, Cosgrove D, Knight R, Barker P, Zabludoff S, Agbo F, Oakes P, Senderowicz A (2014) Phase I dose-escalation study of AZD7762, a checkpoint kinase inhibitor, in combination with gemcitabine in US patients with advanced solid tumors. Cancer Chemother Pharmacol 73:539–549

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  157. Li T, Christensen SD, Frankel PH, Margolin KA, Agarwala SS, Luu T, Mack PC, Lara PJ, Gandara DR (2012) A phase II study of cell cycle inhibitor UCN-01 in patients with metastatic melanoma: a California cancer consortium trial. Investig New Drugs 30:741–748

    CrossRef  CAS  Google Scholar 

  158. Rini BI, Weinberg V, Shaw V, Scott J, Bok R, Park JW, Small EJ (2004) Time to disease progression to evaluate a novel protein kinase C inhibitor, UCN-01, in renal cell carcinoma. CANCER-AM CANCER SOC 101:90–95

    CAS  Google Scholar 

  159. Cowell IG, Durkacz BW, Tilby MJ (2005) Sensitization of breast carcinoma cells to ionizing radiation by small molecule inhibitors of DNA-dependent protein kinase and ataxia telangiectsia mutated. Biochem Pharmacol 71:13–20

    CrossRef  CAS  PubMed  Google Scholar 

  160. Hickson I, Zhao Y, Richardson CJ, Green SJ, Martin NM, Orr AI, Reaper PM, Jackson SP, Curtin NJ, Smith GC (2004) Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res 64:9152–9159

    CrossRef  CAS  PubMed  Google Scholar 

  161. Rainey MD, Charlton ME, Stanton RV, Kastan MB (2008) Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation. Cancer Res 68:7466–7474

    CrossRef  CAS  PubMed  PubMed Central  Google Scholar 

  162. Mack PC, Jones AA, Gustafsson MH, Gandara DR, Gumerlock PH, Goldberg Z (2004) Enhancement of radiation cytotoxicity by UCN-01 in non-small cell lung carcinoma cells. Radiat Res 162:623–634

    CrossRef  CAS  PubMed  Google Scholar 

  163. Ree AH, Bratland A, Nome RV, Stokke T, Fodstad O, Andersson Y (2004) Inhibitory targeting of checkpoint kinase signaling overrides radiation-induced cell cycle gene regulation: a therapeutic strategy in tumor cell radiosensitization? Radiother Oncol 72:305–310

    CrossRef  CAS  PubMed  Google Scholar 

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Acknowledgments

This work has been supported by grants from the National Key R&D Program (2016YFC1302301), Natural Science Foundation of China (81672738).

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Authors and Affiliations

  1. Department of Radiotherapy, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

    Yanhui Jiang & Yimin Liu

  2. Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, 510120, China

    Hai Hu

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  1. Yanhui Jiang
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Correspondence to Yimin Liu .

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  1. Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China

    Erwei Song

  2. Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China

    Hai Hu

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Jiang, Y., Liu, Y., Hu, H. (2017). Studies on DNA Damage Repair and Precision Radiotherapy for Breast Cancer. In: Song, E., Hu, H. (eds) Translational Research in Breast Cancer. Advances in Experimental Medicine and Biology, vol 1026. Springer, Singapore. https://doi.org/10.1007/978-981-10-6020-5_5

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