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Review Article

Targeting DNA Double-Strand Break (DSB) Repair to Counteract Tumor Radio-resistance

Author(s): Yucui Zhao and Siyu Chen*

Volume 20, Issue 9, 2019

Page: [891 - 902] Pages: 12

DOI: 10.2174/1389450120666190222181857

Price: $65

Abstract

During the last decade, advances of radiotherapy (RT) have been made in the clinical practice of cancer treatment. RT exerts its anticancer effect mainly via leading to the DNA Double-Strand Break (DSB), which is one of the most toxic DNA damages. Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR) are two major DSB repair pathways in human cells. It is known that dysregulations of DSB repair elicit a predisposition to cancer and probably result in resistance to cancer therapies including RT. Therefore, targeting the DSB repair presents an attractive strategy to counteract radio-resistance. In this review, we describe the latest knowledge of the two DSB repair pathways, focusing on several key proteins contributing to the repair, such as DNA-PKcs, RAD51, MRN and PARP1. Most importantly, we discuss the possibility of overcoming radiation resistance by targeting these proteins for therapeutic inhibition. Recent tests of DSB repair inhibitors in the laboratory and their translations into clinical studies are also addressed.

Keywords: DNA double-strand break repair, radiotherapy, radio-resistance, radio-sensitizer, molecular targeting, combination therapy.

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[1]
Krause M, Supiot S. Advances in radiotherapy special feature. Br J Radiol 2015; 88(1051): 20150412.
[http://dx.doi.org/10.1259/bjr.20150412] [PMID: 26084353]
[2]
Razmik Mirzayans DM. Role of Therapy-Induced Cellular Senescence in Tumor Cells and its Modification in Radiotherapy: The Good, The Bad and The Ugly. J Nuclear Med Radiation Ther 2013; s6(01)
[3]
Ahmad SS, Duke S, Jena R, Williams MV, Burnet NG. Advances in radiotherapy. BMJ 2012; 345e7765
[http://dx.doi.org/10.1136/ bmj.e7765] [PMID: 23212681]
[4]
Willers H, Azzoli CG, Santivasi WL, Xia F. Basic mechanisms of therapeutic resistance to radiation and chemotherapy in lung cancer. Cancer J 2013; 19(3): 200-7.
[http://dx.doi.org/10.1097/PPO.0b013e318292e4e3] [PMID: 23708066]
[5]
Kim BM, Hong Y, Lee S, et al. Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy. Int J Mol Sci 2015; 16(11): 26880-913.
[http://dx.doi.org/10.3390/ijms 161125991] [PMID: 26569225]
[6]
Srivastava M, Raghavan SC. DNA double-strand break repair inhibitors as cancer therapeutics. Chem Biol 2015; 22(1): 17-29.
[http://dx.doi.org/10.1016/j.chembiol.2014.11.013] [PMID: 25579208]
[7]
Gachechiladze M, Škarda J, Soltermann A, Joerger M. RAD51 as a potential surrogate marker for DNA repair capacity in solid malignancies. Int J Cancer 2017; 141(7): 1286-94.
[http://dx.doi.org/ 10.1002/ijc.30764] [PMID: 28477336]
[8]
Curtin NJ. DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer 2012; 12(12): 801-17.
[http://dx.doi.org/10.1038/nrc3399] [PMID: 23175119]
[9]
Maier P, Hartmann L, Wenz F, Herskind C. Cellular pathways in response to ionizing radiation and their targetability for tumor radiosensitization. Int J Mol Sci 2016; 17(1): E102.
[http://dx.doi.org/10.3390/ijms17010102] [PMID: 26784176]
[10]
Liu C, Srihari S, Cao KA, et al. A fine-scale dissection of the DNA double-strand break repair machinery and its implications for breast cancer therapy. Nucleic Acids Res 2014; 42(10): 6106-27.
[http://dx.doi.org/10.1093/nar/gku284] [PMID: 24792170]
[11]
Chang HHY, Pannunzio NR, Adachi N, Lieber MR. Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat Rev Mol Cell Biol 2017; 18(8): 495-506.
[http://dx.doi.org/10.1038/nrm.2017.48] [PMID: 28512351]
[12]
Seol JH, Shim EY, Lee SE. Microhomology-mediated end joining: Good, bad and ugly. Mutat Res 2018; 809: 81-7.
[http://dx.doi.org/10.1016/j.mrfmmm.2017.07.002] [PMID: 28754468]
[13]
Goglia AG, Delsite R, Luz AN, et al. Identification of novel radiosensitizers in a high-throughput, cell-based screen for DSB repair inhibitors. Mol Cancer Ther 2015; 14(2): 326-42.
[http://dx.doi.org/ 10.1158/1535-7163.MCT-14-0765] [PMID: 25512618]
[14]
Talens F, Jalving M, Gietema JA, Van Vugt MA. Therapeutic targeting and patient selection for cancers with homologous recombination defects. Expert Opin Drug Discov 2017; 12(6): 565-81.
[http://dx.doi.org/10.1080/17460441.2017.1322061] [PMID: 28425306]
[15]
Kaniecki K, De Tullio L, Gibb B, Kwon Y, Sung P, Greene EC. Dissociation of Rad51 Presynaptic Complexes and Heteroduplex DNA Joints by Tandem Assemblies of Srs2. Cell Reports 2017; 21(11): 3166-77.
[http://dx.doi.org/10.1016/j.celrep.2017.11.047] [PMID: 29241544]
[16]
Bartosova Z, Krejci L. Nucleases in homologous recombination as targets for cancer therapy. FEBS Lett 2014; 588(15): 2446-56.
[http://dx.doi.org/10.1016/j.febslet.2014.06.010] [PMID: 24928444]
[17]
Chang L, Huang J, Wang K, et al. Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy. BMC Cancer 2016; 16: 190.
[http://dx.doi.org/10.1186/s12885-016-2190-8] [PMID: 26951044]
[18]
Budke B, Lv W, Kozikowski AP, Connell PP. Recent Developments Using Small Molecules to Target RAD51: How to Best Modulate RAD51 for Anticancer Therapy? ChemMedChem 2016; 11(22): 2468-73.
[http://dx.doi.org/10.1002/cmdc.201600426] [PMID: 27781374]
[19]
Ciszewski WM, Tavecchio M, Dastych J, Curtin NJ. DNA-PK inhibition by NU7441 sensitizes breast cancer cells to ionizing radiation and doxorubicin. Breast Cancer Res Treat 2014; 143(1): 47-55.
[http://dx.doi.org/10.1007/s10549-013-2785-6] [PMID: 24292814]
[20]
Samadder P, Aithal R, Belan O, Krejci L. Cancer TARGETases: DSB repair as a pharmacological target. Pharmacol Ther 2016; 161: 111-31.
[http://dx.doi.org/10.1016/j.pharmthera.2016.02.007] [PMID: 26899499]
[21]
Shen Y, Wang Y, Sheng K, et al. Serine/threonine protein phosphatase 6 modulates the radiation sensitivity of glioblastoma. Cell Death Dis 2011; 2e241
[http://dx.doi.org/10.1038/cddis.2011.126] [PMID: 22158480]
[22]
Sirzén F, Nilsson A, Zhivotovsky B, Lewensohn R. DNA-dependent protein kinase content and activity in lung carcinoma cell lines: correlation with intrinsic radiosensitivity. Eur J Cancer 1999; 35(1): 111-6.
[http://dx.doi.org/10.1016/S0959-8049(98) 00289-5] [PMID: 10211098]
[23]
Yang L, Liu Y, Sun C, et al. Inhibition of DNA-PKcs enhances radiosensitivity and increases the levels of ATM and ATR in NSCLC cells exposed to carbon ion irradiation. Oncol Lett 2015; 10(5): 2856-64.
[http://dx.doi.org/10.3892/ol.2015.3730] [PMID: 26722253]
[24]
Ma H, Takahashi A, Yoshida Y, et al. Combining carbon ion irradiation and non-homologous end-joining repair inhibitor NU7026 efficiently kills cancer cells. Radiat Oncol 2015; 10: 225.
[http://dx.doi.org/10.1186/s13014-015-0536-z] [PMID: 26553138]
[25]
Li Y, Li H, Peng W, et al. DNA-dependent protein kinase catalytic subunit inhibitor reverses acquired radioresistance in lung adenocarcinoma by suppressing DNA repair. Mol Med Rep 2015; 12(1): 1328-34.
[http://dx.doi.org/10.3892/mmr.2015.3505] [PMID: 25815686]
[26]
Dolman MEM, van der Ploeg I, Koster J, et al. DNA-dependent protein kinase as molecular target for radiosensitization of neuroblastoma cells. PLoS One 2015; 10(12): e0145744.
[http://dx.doi.org/10.1371/journal.pone.0145744] [PMID: 26716839]
[27]
Dong J, Ren Y, Zhang T, et al. Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair. Oncol Rep 2018; 39(3): 912-20.
[http://dx.doi.org/10.3892/or.2018.6217] [PMID: 29344644]
[28]
Hsu FM, Zhang S, Chen BP. Role of DNA-dependent protein kinase catalytic subunit in cancer development and treatment. Transl Cancer Res 2012; 1(1): 22-34.
[PMID: 22943041]
[29]
Langland GT, Yannone SM, Langland RA, et al. Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities. Oncol Rep 2010; 23(4): 1021-6.
[http://dx.doi.org/ 10.3892/or_00000728] [PMID: 20204287]
[30]
Stronach EA, Chen M, Maginn EN, et al. DNA-PK mediates AKT activation and apoptosis inhibition in clinically acquired platinum resistance. Neoplasia 2011; 13(11): 1069-80.
[http://dx.doi.org/10.1593/neo.111032] [PMID: 22131882]
[31]
Lafrance-Vanasse J, Williams GJ, Tainer JA. Envisioning the dynamics and flexibility of Mre11-Rad50-Nbs1 complex to decipher its roles in DNA replication and repair. Prog Biophys Mol Biol 2015; 117(2-3): 182-93.
[http://dx.doi.org/10.1016/j.pbiomolbio. 2014.12.004] [PMID: 25576492]
[32]
Shibata A. Regulation of repair pathway choice at two-ended DNA double-strand breaks. Mutat Res 2017; 803-805: 51-5.
[http://dx.doi.org/10.1016/j.mrfmmm.2017.07.011] [PMID: 28781144]
[33]
Saito Y, Komatsu K. Functional Role of NBS1 in Radiation Damage Response and Translesion DNA Synthesis. Biomolecules 2015; 5(3): 1990-2002.
[http://dx.doi.org/10.3390/biom5031990] [PMID: 26308066]
[34]
Stracker TH, Petrini JH. The MRE11 complex: starting from the ends. Nat Rev Mol Cell Biol 2011; 12(2): 90-103.
[http://dx.doi.org/10.1038/nrm3047] [PMID: 21252998]
[35]
Spehalski E, Capper KM, Smith CJ, et al. MRE11 Promotes Tumorigenesis by Facilitating Resistance to Oncogene-Induced Replication Stress. Cancer Res 2017; 77(19): 5327-38.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-1355] [PMID: 28819025]
[36]
Kim BM, Hong Y, Lee S, et al. Therapeutic Implications for Overcoming Radiation Resistance in Cancer Therapy. Int J Mol Sci 2015; 16(11): 26880-913.
[http://dx.doi.org/10.3390/ijms 161125991] [PMID: 26569225]
[37]
Yuan SSF, Hou MF, Hsieh YC, et al. Role of MRE11 in cell proliferation, tumor invasion, and DNA repair in breast cancer. J Natl Cancer Inst 2012; 104(19): 1485-502.
[http://dx.doi.org/10.1093/jnci/djs355] [PMID: 22914783]
[38]
Petroni M, Sardina F, Infante P, et al. MRE11 inhibition highlights a replication stress-dependent vulnerability of MYCN-driven tumors. Cell Death Dis 2018; 9(9): 895.
[http://dx.doi.org/10.1038/s41419-018-0924-z] [PMID: 30166519]
[39]
Yang MH, Chang SY, Chiou SH, et al. Overexpression of NBS1 induces epithelial-mesenchymal transition and co-expression of NBS1 and Snail predicts metastasis of head and neck cancer. Oncogene 2007; 26(10): 1459-67.
[http://dx.doi.org/10.1038/sj.onc. 1209929] [PMID: 16936774]
[40]
Schlacher K, Wu H, Jasin M. A distinct replication fork protection pathway connects Fanconi anemia tumor suppressors to RAD51-BRCA1/2. Cancer Cell 2012; 22(1): 106-16.
[http://dx.doi.org/ 10.1016/j.ccr.2012.05.015] [PMID: 22789542]
[41]
Qiao GB, Wu YL, Yang XN, et al. High-level expression of Rad51 is an independent prognostic marker of survival in non-small-cell lung cancer patients. Br J Cancer 2005; 93(1): 137-43.
[http://dx.doi.org/10.1038/sj.bjc.6602665] [PMID: 15956972]
[42]
Tennstedt P, Fresow R, Simon R, et al. RAD51 overexpression is a negative prognostic marker for colorectal adenocarcinoma. Int J Cancer 2013; 132(9): 2118-26.
[http://dx.doi.org/10.1002/ijc.27907] [PMID: 23065657]
[43]
Ito M, Yamamoto S, Nimura K, Hiraoka K, Tamai K, Kaneda Y. Rad51 siRNA delivered by HVJ envelope vector enhances the anti-cancer effect of cisplatin. J Gene Med 2005; 7(8): 1044-52.
[http://dx.doi.org/10.1002/jgm.753] [PMID: 15756713]
[44]
Gasparini P, Lovat F, Fassan M, et al. Protective role of miR-155 in breast cancer through RAD51 targeting impairs homologous recombination after irradiation. Proc Natl Acad Sci USA 2014; 111(12): 4536-41.
[http://dx.doi.org/10.1073/pnas.1402604111] [PMID: 24616504]
[45]
Piotto C, Biscontin A, Millino C, Mognato M. Functional validation of miRNAs targeting genes of DNA double-strand break repair to radiosensitize non-small lung cancer cells. Biochim Biophys Acta Gene Regul Mech 2018; 1861(12): 1102-18.
[http://dx.doi.org/10.1016/j.bbagrm.2018.10.010] [PMID: 30389599]
[46]
Palazzo L, Ahel I. PARPs in genome stability and signal transduction: implications for cancer therapy. Biochem Soc Trans 2018; 46(6): 1681-95.
[http://dx.doi.org/10.1042/BST20180418] [PMID: 30420415]
[47]
Prasad CB, Prasad SB, Yadav SS, et al. Olaparib modulates DNA repair efficiency, sensitizes cervical cancer cells to cisplatin and exhibits anti-metastatic property. Sci Rep 2017; 7(1): 12876.
[http://dx.doi.org/10.1038/s41598-017-13232-3] [PMID: 28993682]
[48]
Rosen EM, Pishvaian MJ. Targeting the BRCA1/2 tumor suppressors. Curr Drug Targets 2014; 15(1): 17-31.
[http://dx.doi.org/10.2174/1389450114666140106095432] [PMID: 24387 337]
[49]
Ossovskaya V, Koo IC, Kaldjian EP, Alvares C, Sherman BM. Upregulation of poly (ADP-Ribose) polymerase-1 (PARP1) in triple-negative breast cancer and other primary human tumor types. Genes Cancer 2010; 1(8): 812-21.
[http://dx.doi.org/ 10.1177/1947601910383418] [PMID: 21779467]
[50]
Ray Chaudhuri A, Nussenzweig A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat Rev Mol Cell Biol 2017; 18(10): 610-21.
[http://dx.doi.org/10.1038/nrm.2017.53] [PMID: 28676700]
[51]
Byers LA, Wang J, Nilsson MB, et al. Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1. Cancer Discov 2012; 2(9): 798-811.
[http://dx.doi.org/10.1158/2159-8290.CD-12-0112] [PMID: 22961666]
[52]
Wang L, Liang C, Li F, et al. PARP1 in carcinomas and PARP1 inhibitors as antineoplastic drugs. Int J Mol Sci 2017; 18(10): E2111.
[http://dx.doi.org/10.3390/ijms18102111] [PMID: 28991194]
[53]
Weaver AN, Yang ES. Beyond DNA repair: Additional functions of PARP-1 in cancer. Front Oncol 2013; 3: 290.
[http://dx.doi.org/10.3389/fonc.2013.00290] [PMID: 24350055]
[54]
Ramakrishnan Geethakumari P, Schiewer MJ, Knudsen KE, Kelly WK. PARP inhibitors in prostate cancer. Curr Treat Options Oncol 2017; 18(6): 37.
[http://dx.doi.org/10.1007/s11864-017-0480-2] [PMID: 28540598]
[55]
Bryant HE, Schultz N, Thomas HD, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005; 434(7035): 913-7.
[http://dx.doi.org/ 10.1038/nature03443] [PMID: 15829966]
[56]
Farmer H, McCabe N, Lord CJ, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005; 434(7035): 917-21.
[http://dx.doi.org/10.1038/nature03445] [PMID: 15829967]
[57]
Murai J, Huang SY, Renaud A, et al. Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib. Mol Cancer Ther 2014; 13(2): 433-43.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0803] [PMID: 24356813]
[58]
Sunada S, Nakanishi A, Miki Y. Crosstalk of DNA double-strand break repair pathways in poly(ADP-ribose) polymerase inhibitor treatment of breast cancer susceptibility gene 1/2-mutated cancer. Cancer Sci 2018; 109(4): 893-9.
[http://dx.doi.org/10.1111/cas.13530] [PMID: 29427345]
[59]
Lesueur P, Chevalier F, Austry JB, et al. Poly-(ADP-ribose)-polymerase inhibitors as radiosensitizers: A systematic review of pre-clinical and clinical human studies. Oncotarget 2017; 8(40): 69105-24.
[http://dx.doi.org/10.18632/oncotarget.19079] [PMID: 28978184]
[60]
Morgan MA, Lawrence TS. Molecular pathways: Overcoming radiation resistance by targeting DNA damage response pathways. Clin Cancer Res 2015; 21(13): 2898-904.
[http://dx.doi.org/ 10.1158/1078-0432.CCR-13-3229] [PMID: 26133775]
[61]
Herrera FG, Bourhis J, Coukos G. Radiotherapy combination opportunities leveraging immunity for the next oncology practice. CA Cancer J Clin 2017; 67(1): 65-85.
[http://dx.doi.org/10.3322/caac.21358] [PMID: 27570942]
[62]
Schenone M, Dančík V, Wagner BK, Clemons PA. Target identification and mechanism of action in chemical biology and drug discovery. Nat Chem Biol 2013; 9(4): 232-40.
[http://dx.doi.org/ 10.1038/nchembio.1199] [PMID: 23508189]
[63]
Sallán MC, Visa A, Shaikh S, Nàger M, Herreros J, Cantí C. T-type Ca2+ Channels: T for Targetable. Cancer Res 2018; 78(3): 603-9.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-3061] [PMID: 29343521]
[64]
Davidson D, Amrein L, Panasci L, Aloyz R. Small molecules, inhibitors of DNA-PK, targeting DNA repair, and beyond. Front Pharmacol 2013; 4: 5.
[http://dx.doi.org/10.3389/fphar.2013.00005] [PMID: 23386830]
[65]
Goodwin JF, Knudsen KE. Beyond DNA repair: DNA-PK function in cancer. Cancer Discov 2014; 4(10): 1126-39.
[http://dx.doi.org/10.1158/2159-8290.CD-14-0358] [PMID: 25168287]
[66]
Zhao W, Qiu Y, Kong D. Class I phosphatidylinositol 3-kinase inhibitors for cancer therapy. Acta Pharm Sin B 2017; 7(1): 27-37.
[http://dx.doi.org/10.1016/j.apsb.2016.07.006] [PMID: 28119806]
[67]
Anzai K, Sekine-Suzuki E, Ueno M, et al. Effectiveness of combined treatment using X-rays and a phosphoinositide 3-kinase inhibitor, ZSTK474, on proliferation of HeLa cells in vitro and in vivo. Cancer Sci 2011; 102(6): 1176-80.
[http://dx.doi.org/ 10.1111/j.1349-7006.2011.01916.x] [PMID: 21352422]
[68]
Le Tourneau C, Dreno B, Kirova Y, et al. First-in-human phase I study of the DNA-repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma. Br J Cancer 2016; 114(11): 1199-205.
[http://dx.doi.org/10.1038/bjc. 2016.120] [PMID: 27140316]
[69]
Huang F, Mazina OM, Zentner IJ, Cocklin S, Mazin AV. Inhibition of homologous recombination in human cells by targeting RAD51 recombinase. J Med Chem 2012; 55(7): 3011-20.
[http://dx.doi.org/ 10.1021/jm201173g] [PMID: 22380680]
[70]
Huang F, Motlekar NA, Burgwin CM, Napper AD, Diamond SL, Mazin AV. Identification of specific inhibitors of human RAD51 recombinase using high-throughput screening. ACS Chem Biol 2011; 6(6): 628-35.
[http://dx.doi.org/10.1021/cb100428c] [PMID: 21428443]
[71]
Budke B, Logan HL, Kalin JH, et al. RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells. Nucleic Acids Res 2012; 40(15): 7347-57.
[http://dx.doi.org/ 10.1093/nar/gks353] [PMID: 22573178]
[72]
Budke B, Kalin JH, Pawlowski M, et al. An optimized RAD51 inhibitor that disrupts homologous recombination without requiring Michael acceptor reactivity. J Med Chem 2013; 56(1): 254-63.
[http://dx.doi.org/10.1021/jm301565b] [PMID: 23231413]
[73]
King HO, Brend T, Payne HL, et al. RAD51 Is a Selective DNA Repair Target to Radiosensitize Glioma Stem Cells. Stem Cell Reports 2017; 8(1): 125-39.
[http://dx.doi.org/10.1016/j.stemcr.2016. 12.005] [PMID: 28076755]
[74]
Ward A, Khanna KK, Wiegmans AP. Targeting homologous recombination, new pre-clinical and clinical therapeutic combinations inhibiting RAD51. Cancer Treat Rev 2015; 41(1): 35-45.
[http://dx.doi.org/10.1016/j.ctrv.2014.10.006] [PMID: 25467108]
[75]
Zhao H, Luoto KR, Meng AX, Bristow RG. The receptor tyrosine kinase inhibitor amuvatinib (MP470) sensitizes tumor cells to radio- and chemo-therapies in part by inhibiting homologous recombination. Radiother Oncol 2011; 101(1): 59-65.
[http://dx.doi.org/ 10.1016/j.radonc.2011.08.013] [PMID: 21903282]
[76]
Mita M, Gordon M, Rosen L, et al. Phase 1B study of amuvatinib in combination with five standard cancer therapies in adults with advanced solid tumors. Cancer Chemother Pharmacol 2014; 74(1): 195-204.
[http://dx.doi.org/10.1007/s00280-014-2481-1] [PMID: 24849582]
[77]
Shoji M, Ninomiya I, Makino I, et al. Valproic acid, a histone deacetylase inhibitor, enhances radiosensitivity in esophageal squamous cell carcinoma. Int J Oncol 2012; 40(6): 2140-6.
[http://dx.doi.org/10.3892/ijo.2012.1416] [PMID: 22469995]
[78]
Luo Y, Wang H, Zhao X, et al. Valproic acid causes radiosensitivity of breast cancer cells via disrupting the DNA repair pathway. Toxicol Res (Camb) 2016; 5(3): 859-70.
[http://dx.doi.org/ 10.1039/C5TX00476D] [PMID: 30090395]
[79]
Ochiai S, Nomoto Y, Yamashita Y, et al. Roles of Valproic Acid in Improving Radiation Therapy for Glioblastoma: a Review of Literature Focusing on Clinical Evidence. Asian Pac J Cancer Prev 2016; 17(2): 463-6.
[http://dx.doi.org/10.7314/APJCP.2016.17. 2.463] [PMID: 26925628]
[80]
Liu G, Wang H, Zhang F, et al. The Effect of VPA on Increasing Radiosensitivity in Osteosarcoma Cells and Primary-Culture Cells from Chemical Carcinogen-Induced Breast Cancer in Rats. Int J Mol Sci 2017; 18(5): E1027.
[http://dx.doi.org/10.3390/ijms 18051027] [PMID: 28489060]
[81]
Krauze AV, Mackey M, Rowe L, et al. Late toxicity in long-term survivors from a phase 2 study of concurrent radiation therapy, temozolomide and valproic acid for newly diagnosed glioblastoma. Neurooncol Pract 2018; 5(4): 246-50.
[http://dx.doi.org/10.1093/nop/npy009] [PMID: 30402263]
[82]
Krauze AV, Myrehaug SD, Chang MG, et al. A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma. Int J Radiat Oncol Biol Phys 2015; 92(5): 986-92.
[http://dx.doi.org/10.1016/j.ijrobp.2015.04.038] [PMID: 26194676]
[83]
Dupre A, et al. A forward chemical genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex (vol 4, pg 119, 2008). Nat Chem Biol 2009; 5(3): 191-.
[http://dx.doi.org/10.1038/nchembio 0309-191a]
[84]
Ohara M, Funyu Y, Ebara S, et al. Mutations in the FHA-domain of ectopically expressed NBS1 lead to radiosensitization and to no increase in somatic mutation rates via a partial suppression of homologous recombination. J Radiat Res (Tokyo) 2014; 55(4): 690-8.
[http://dx.doi.org/10.1093/jrr/rru011] [PMID: 24614819]
[85]
Kuroda S, Urata Y, Fujiwara T. Ataxia-telangiectasia mutated and the Mre11-Rad50-NBS1 complex: promising targets for radiosensitization. Acta Med Okayama 2012; 66(2): 83-92.
[PMID: 2252 5466]
[86]
Kuroda S, Fujiwara T, Shirakawa Y, et al. Telomerase-dependent oncolytic adenovirus sensitizes human cancer cells to ionizing radiation via inhibition of DNA repair machinery. Cancer Res 2010; 70(22): 9339-48.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2333] [PMID: 21045143]
[87]
Taguchi S, Fukuhara H, Todo T. Oncolytic virus therapy in Japan: progress in clinical trials and future perspectives. Jpn J Clin Oncol 2018.
[PMID: 30462296]
[88]
Purnell MR, Whish WJ. Novel inhibitors of poly(ADP-ribose) synthetase. Biochem J 1980; 185(3): 775-7.
[http://dx.doi.org/ 10.1042/bj1850775] [PMID: 6248035]
[89]
Lord CJ, Ashworth A. PARP inhibitors: Synthetic lethality in the clinic. Science 2017; 355(6330): 1152-8.
[http://dx.doi.org/ 10.1126/science.aam7344] [PMID: 28302823]
[90]
Bitler BG, Watson ZL, Wheeler LJ, Behbakht K. PARP inhibitors: Clinical utility and possibilities of overcoming resistance. Gynecol Oncol 2017; 147(3): 695-704.
[http://dx.doi.org/10.1016/j.ygyno. 2017.10.003] [PMID: 29037806]
[91]
Kunze FA, Hottiger MO. Hottiger, Regulating Immunity via ADP-Ribosylation: Thera-peutic Implications and Beyond. Trends Immunol 2019.
[92]
Verhagen CVM, de Haan R, Hageman F, et al. Extent of radiosensitization by the PARP inhibitor olaparib depends on its dose, the radiation dose and the integrity of the homologous recombination pathway of tumor cells. Radiother Oncol 2015; 116(3): 358-65.
[http://dx.doi.org/10.1016/j.radonc.2015.03.028] [PMID: 25981132]
[93]
Karam SD, Reddy K, Blatchford PJ, et al. Final Report of a Phase I Trial of Olaparib with Cetuximab and Radiation for Heavy Smoker Patients with Locally Advanced Head and Neck Cancer. Clin Cancer Res 2018; 24(20): 4949-59.
[http://dx.doi.org/10.1158/1078-0432.CCR-18-0467] [PMID: 30084837]
[94]
Jue TR, Nozue K, Lester AJ, et al. Veliparib in combination with radiotherapy for the treatment of MGMT unmethylated glioblastoma. J Transl Med 2017; 15(1): 61.
[http://dx.doi.org/10.1186/s12967-017-1164-1] [PMID: 28314386]
[95]
Shelton JW, Waxweiler TV, Landry J, et al. In vitro and in vivo enhancement of chemoradiation using the oral PARP inhibitor ABT-888 in colorectal cancer cells. Int J Radiat Oncol Biol Phys 2013; 86(3): 469-76.
[http://dx.doi.org/10.1016/j.ijrobp.2013.02. 015] [PMID: 23540347]
[96]
Owonikoko TK, Zhang G, Deng X, et al. Poly (ADP) ribose polymerase enzyme inhibitor, veliparib, potentiates chemotherapy and radiation in vitro and in vivo in small cell lung cancer. Cancer Med 2014; 3(6): 1579-94.
[http://dx.doi.org/10.1002/cam4.317] [PMID: 25124282]
[97]
Czito BG, Deming DA, Jameson GS, et al. Safety and tolerability of veliparib combined with capecitabine plus radiotherapy in patients with locally advanced rectal cancer: a phase 1b study. Lancet Gastroenterol Hepatol 2017; 2(6): 418-26.
[http://dx.doi.org/ 10.1016/S2468-1253(17)30012-2] [PMID: 28497757]
[98]
Tuli R, Shiao SL, Nissen N, et al. A phase 1 study of veliparib, a PARP-1/2 inhibitor, with gemcitabine and radiotherapy in locally advanced pancreatic cancer. EBioMedicine 2019; 40: 375-81.
[http://dx.doi.org/10.1016/j.ebiom.2018.12.060] [PMID: 30635165]
[99]
Sun K, Mikule K, Wang Z, et al. A comparative pharmacokinetic study of PARP inhibitors demonstrates favorable properties for niraparib efficacy in preclinical tumor models. Oncotarget 2018; 9(98): 37080-96.
[http://dx.doi.org/10.18632/oncotarget.26354] [PMID: 30647846]
[100]
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(19): 6106-12.
[http://dx.doi.org/ 10.1158/1078-0432.CCR-09-0398] [PMID: 19789326]
[101]
Durisova K, Salovska B, Pejchal J, Tichy A. Chemical inhibition of DNA repair kinases as a promising tool in oncology. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016; 160(1): 11-9.
[http://dx.doi.org/10.5507/bp.2015.046] [PMID: 26498210]
[102]
Dungl DA, Maginn EN, Stronach EA. Preventing Damage Limitation: Targeting DNA-PKcs and DNA Double-Strand Break Repair Pathways for Ovarian Cancer Therapy. Front Oncol 2015; 5: 240.
[http://dx.doi.org/10.3389/fonc.2015.00240] [PMID: 26579492]
[103]
Liu Y, Zhang L, Liu Y, et al. DNA-PKcs deficiency inhibits glioblastoma cell-derived angiogenesis after ionizing radiation. J Cell Physiol 2015; 230(5): 1094-103.
[http://dx.doi.org/10.1002/jcp. 24841] [PMID: 25294801]
[104]
Sunada S, Kanai H, Lee Y, et al. Nontoxic concentration of DNA-PK inhibitor NU7441 radio-sensitizes lung tumor cells with little effect on double strand break repair. Cancer Sci 2016; 107(9): 1250-5.
[http://dx.doi.org/10.1111/cas.12998] [PMID: 27341700]
[105]
Zhao Y, Thomas HD, Batey MA, et al. Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Res 2006; 66(10): 5354-62.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-4275] [PMID: 16707462]
[106]
Huang F, Mazin AV. A small molecule inhibitor of human RAD51 potentiates breast cancer cell killing by therapeutic agents in mouse xenografts. PLoS One 2014; 9(6): e100993.
[http://dx.doi.org/ 10.1371/journal.pone.0100993] [PMID: 24971740]
[107]
Ward A, Khanna KK, Wiegmans AP. Targeting homologous recombination, new pre-clinical and clinical therapeutic combinations inhibiting RAD51. Cancer Treat Rev 2015; 41(1): 35-45.
[http://dx.doi.org/10.1016/j.ctrv.2014.10.006] [PMID: 25467108]

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