Hyperthermia-induced DNA repair deficiency suggests novel therapeutic anti-cancer strategies

References

• Stege GJ, Kampinga HH, Konings AW. Heat-induced intranuclear protein aggregation and thermal radiosensitization. Int J Radiat Biol 1995; 67: 203–209
   PubMed Web of Science ®Google Scholar
• Beck BD, Dynlacht JR. Heat-induced aggregation of XRCC5 (Ku80) in nontolerant and thermotolerant cells. Radiat Res 2001; 156: 767–774
   PubMed Web of Science ®Google Scholar
• Laszlo A, Davidson T, Harvey A, Sim JE, Malyapa RS, Spitz DR, et al. Alterations in heat-induced radiosensitization accompanied by nuclear structure alterations in Chinese hamster cells. Int J Hyperthermia 2006; 22: 43–60
   PubMed Web of Science ®Google Scholar
• Hanada K, Budzowska M, Modesti M, Maas A, Wyman C, Essers J, et al. The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks. Embo J 2006; 25: 4921–4932
   PubMed Web of Science ®Google Scholar
• Drablos F, Feyzi E, Aas PA, Vaagbo CB, Kavli B, Bratlie MS, et al. Alkylation damage in DNA and RNA-repair mechanisms and medical significance. DNA Repair (Amst) 2004; 3: 1389–1407
   PubMed Web of Science ®Google Scholar
• Gupta R, Brosh RM, Jr. DNA repair helicases as targets for anti-cancer therapy. Cur Med Chem 2007; 14: 503–517
   PubMed Web of Science ®Google Scholar
• Galmarini CM, Popowycz F, Joseph B. Cytotoxic nucleoside analogues: Different strategies to improve their clinical efficacy. Cur Med Chem 2008; 15: 1072–1082
   PubMed Web of Science ®Google Scholar
• Wheate NJ, Brodie CR, Collins JG, Kemp S, Aldrich-Wright JR. DNA intercalators in cancer therapy: Organic and inorganic drugs and their spectroscopic tools of analysis. Mini Rev Med Chem 2007; 7: 627–648
   PubMed Web of Science ®Google Scholar
• Weterings E, Chen DJ. The endless tale of non-homologous end-joining. Cell Res 2008; 18: 114–124
   PubMed Web of Science ®Google Scholar
• Ahnesorg P, Smith P, Jackson SP. XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell 2006; 124: 301–313
   PubMed Web of Science ®Google Scholar
• Smith GC, Divecha N, Lakin ND, Jackson SP. DNA-dependent protein kinase and related proteins. Biochem Soc Symp 1999; 64: 91–104
   PubMedGoogle Scholar
• Cui X, Yu Y, Gupta S, Cho YM, Lees-Miller SP, Meek K. Autophosphorylation of DNA-dependent protein kinase regulates DNA end processing and may also alter double strand break repair pathway choice. Mol Cell Biol 2005; 25: 10842–10852
   PubMed Web of Science ®Google Scholar
• Meek K, Douglas P, Cui X, Ding Q, Lees-Miller SP. trans Autophosphorylation at DNA-dependent protein kinase's two major autophosphorylation site clusters facilitates end processing but not end joining. Mol Cell Biol 2007; 27: 3881–3890
   PubMed Web of Science ®Google Scholar
• Goodarzi AA, Yu Y, Riballo E, Douglas P, Walker SA, Ye R, et al. DNA-PK autophosphorylation facilitates Artemis endonuclease activity. Embo J 2006; 25: 3880–3889
   PubMed Web of Science ®Google Scholar
• Darroudi F, Wiegant W, Meijers M, Friedl AA, van der Burg M, Fomina J, et al. Role of Artemis in DSB repair and guarding chromosomal stability following exposure to ionizing radiation at different stages of cell cycle. Mutat Res 2007; 615: 111–124
   PubMed Web of Science ®Google Scholar
• van Gent DC, van der Burg M. Non-homologous end-joining, a sticky affair. Oncogene 2007; 26: 7731–7740
   PubMed Web of Science ®Google Scholar
• Tsai CJ, Kim SA, Chu G. Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends. Proc Natl Acad Sci USA 2007; 104: 7851–7856
   PubMed Web of Science ®Google Scholar
• Wu PY, Frit P, Malivert L, Revy P, Biard D, Salles B, et al. Interplay between Cernunnos-XLF and nonhomologous end-joining proteins at DNA ends in the cell. J Biol Chem 2007; 282: 31937–31943
   PubMed Web of Science ®Google Scholar
• Tashiro S, Walter J, Shinohara A, Kamada N, Cremer T. Rad51 accumulation at sites of DNA damage and in post replicative chromatin. J Cell Biol 2000; 150: 283–291
   PubMed Web of Science ®Google Scholar
• Cox MM, Goodman MF, Kreuzer KN, Sherratt DJ, Sandler SJ, Marians KJ. The importance of repairing stalled replication forks. Nature 2000; 404: 37–41
   PubMed Web of Science ®Google Scholar
• Eppink B, Wyman C, Kanaar R. Multiple interlinked mechanisms to circumvent DNA replication roadblocks. Exp Cell Res 2006; 312: 2660–2665
   PubMed Web of Science ®Google Scholar
• Kowalczykowski SC. Initiation of genetic recombination and recombination dependent replication. Trends Biochem Sci 2000; 25: 156–165
   PubMed Web of Science ®Google Scholar
• Wyman C, Kanaar R. DNA double-strand break repair: All's well that ends well. Annu Rev Genet 2006; 40: 363–383
   PubMed Web of Science ®Google Scholar
• Wyman C, Kanaar R. Homologous recombination: Down to the wire. Curr Biol 2004; 14: R629–R631
   PubMed Web of Science ®Google Scholar
• Gudmundsdottir K, Ashworth A. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene 2006; 25: 5864–5874
   PubMed Web of Science ®Google Scholar
• Shivji MK, Venkitaraman AR. DNA recombination, chromosomal stability and carcinogenesis: Insights into the role of BRCA2. DNA Repair (Amst) 2004; 3: 835–843
   PubMed Web of Science ®Google Scholar
• Mackey MA, Dewey WC. Time–temperature analyses of cell killing of synchronous G1 and S phase Chinese hamster cells in vitro. Radiat Res 1988; 113: 318–333
   PubMed Web of Science ®Google Scholar
• Dewey WC, Westra A, Miller HH, Nagasawa H. Heat-induced lethality and chromosomal damage in synchronized Chinese hamster cells treated with 5-bromodeoxyuridine. Int J Radiat Biol Relat Stud Phys Chem Med 1971; 20: 505–520
   PubMed Web of Science ®Google Scholar
• Mackey MA, Anolik SL, Roti Roti JL. Changes in heat and radiation sensitivity during long duration, moderate hyperthermia in HeLa S3 cells. Int J Radiat Oncol Biol Phys 1992; 24: 543–550
   PubMed Web of Science ®Google Scholar
• Mackey MA, Roti Roti JL. A model of heat-induced clonogenic cell death. J Theor Biol 1992; 156: 133–146
   PubMed Web of Science ®Google Scholar
• Dewey WC, Sapareto SA, Betten DA. Hyperthermic radiosensitization of synchronous Chinese hamster cells: Relationship between lethality and chromosomal aberrations. Radiat Res 1978; 76: 48–59
   PubMed Web of Science ®Google Scholar
• Hunt CR, Pandita RK, Laszlo A, Higashikubo R, Agarwal M, Kitamura T, et al. Hyperthermia activates a subset of ataxia-telangiectasia mutated effectors independent of DNA strand breaks and heat shock protein 70 status. Cancer Res 2007; 67: 3010–3017
   PubMed Web of Science ®Google Scholar
• VanderWaal RP, Griffith CL, Wright WD, Borrelli MJ, Roti JL. Delaying S-phase progression rescues cells from heat-induced S-phase hypertoxicity. J Cell Physiol 2001; 187: 236–243
   PubMed Web of Science ®Google Scholar
• Dynlacht JR, Xu M, Pandita RK, Wetzel EA, Roti Roti JL. Effects of heat shock on the MRE11/Rad50/NBS1 complex in irradiated or unirradiated cells. Int J Hyperthermia 2004; 20: 144–156
   PubMed Web of Science ®Google Scholar
• Oza P, Jaspersen SL, Miele A, Dekker J, Peterson CL. Mechanisms that regulate localization of a DNA double-strand break to the nuclear periphery. Genes Dev 2009; 23: 912–927
   PubMed Web of Science ®Google Scholar
• Kalocsay M, Hiller NJ, Jentsch S. Chromosome-wide Rad51 spreading and SUMOH2A. Z-dependent chromosome fixation in response to a persistent DNA double-strand break. Mol Cell 2009; 33: 335–343
   PubMed Web of Science ®Google Scholar
• Agarwal S, van Cappellen WA, Guenole A, Eppink B, Linsen SE, Meijering E, et al. ATP-dependent and independent functions of Rad54 in genome maintenance. J Cell Biol 2011; 192: 735–750
   PubMed Web of Science ®Google Scholar
• Dynlacht JR, Bittner ME, Bethel JA, Beck BD. The non-homologous end-joining pathway is not involved in the radiosensitization of mammalian cells by heat shock. J Cell Physiol 2003; 196: 557–564
   PubMed Web of Science ®Google Scholar
• Kampinga HH, Kanon B, Konings AW, Stackhouse MA, Bedford JS. Thermal radiosensitization in heat- and radiation-sensitive mutants of CHO cells. Int J Radiat Biol 1993; 64: 225–230
   PubMed Web of Science ®Google Scholar
• Raaphorst GP, Thakar M, Ng CE. Thermal radiosensitization in two pairs of CHO wild-type and radiation-sensitive mutant cell lines. Int J Hyperthermia 1993; 9: 383–391
   PubMed Web of Science ®Google Scholar
• Wachters FM, van Putten JW, Maring JG, Zdzienicka MZ, Groen HJ, Kampinga HH. Selective targeting of homologous DNA recombination repair by gemcitabine. Int J Radiat Oncol Biol Phys 2003; 57: 553–562
   PubMed Web of Science ®Google Scholar
• Yin HL, Suzuki Y, Matsumoto Y, Tomita M, Furusawa Y, Enomoto A, et al. Radiosensitization by hyperthermia in the chicken B-lymphocyte cell line DT40 and its derivatives lacking nonhomologous end joining and/or homologous recombination pathways of DNA double-strand break repair. Radiat Res 2004; 162: 433–441
   PubMed Web of Science ®Google Scholar
• Raaphorst GP, Maude-Leblanc J, Li L. Evaluation of recombination repair pathways in thermal radiosensitization. Radiat Res 2004; 161: 215–218
   PubMed Web of Science ®Google Scholar
• Krawczyk PM, Eppink B, Essers J, Stap J, Rodermond H, Odijk H, et al. Mild hyperthermia inhibits homologous recombination, induces BRCA2 degradation, and sensitizes cancer cells to poly (ADP-ribose) polymerase-1 inhibition. Proc Natl Acad Sci USA 2011; 108: 9851–9856
   PubMed Web of Science ®Google Scholar
• Xu M, Myerson RJ, Hunt C, Kumar S, Moros EG, Straube WL, et al. Transfection of human tumour cells with Mre11 siRNA and the increase in radiation sensitivity and the reduction in heat-induced radiosensitization. Int J Hyperthermia 2004; 20: 157–162
   PubMed Web of Science ®Google Scholar
• Essers J, Houtsmuller AB, van Veelen L, Paulusma C, Nigg AL, Pastink A, et al. Nuclear dynamics of Rad52 group homologous recombination proteins in response to DNA damage. Embo J 2002; 21: 2030–2037
   PubMed Web of Science ®Google Scholar
• Thacker J. The Rad51 gene family, genetic instability and cancer. Cancer Lett 2005; 219: 125–135
   PubMed Web of Science ®Google Scholar
• van Veelen LR, Essers J, van de Rakt MW, Odijk H, Pastink A, Zdzienicka MZ, et al. Ionizing radiation-induced foci formation of mammalian Rad51 and Rad54 depends on the Rad51 paralogs, but not on Rad52. Mutat Res 2005; 574: 34–49
   PubMed Web of Science ®Google Scholar
• Aten JA, Stap J, Krawczyk PM, van Oven CH, Hoebe RA, Essers J, et al. Dynamics of DNA double-strand breaks revealed by clustering of damaged chromosome domains. Science 2004; 303: 92–95
   PubMed Web of Science ®Google Scholar
• Stap J, Krawczyk PM, Van Oven CH, Barendsen GW, Essers J, Kanaar R, et al. Induction of linear tracks of DNA double-strand breaks by alpha-particle irradiation of cells. Nat Methods 2008; 5: 261–266
   PubMed Web of Science ®Google Scholar
• Iliakis G, Seaner R. A DNA double-strand break repair-deficient mutant of CHO cells shows reduced radio sensitization after exposure to hyperthermic temperatures in the plateau phase of growth. Int J Hyperthermia 1990; 6: 801–812
   PubMed Web of Science ®Google Scholar
• Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005; 434: 917–921
   PubMed Web of Science ®Google Scholar
• Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 2009; 361: 123–134
   PubMed Web of Science ®Google Scholar
• Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005; 434: 913–917
   PubMed Web of Science ®Google Scholar
• Modi S, Stopeck AT, Gordon MS, Mendelson D, Solit DB, Bagatell R, et al. Combination of trastuzumab and tanespimycin (17-AAG, KOS-953) is safe and active in trastuzumab-refractory HER-2 overexpressing breast cancer: A phase I dose-escalation study. J Clin Oncol 2007; 25: 5410–5417
   PubMed Web of Science ®Google Scholar
• Plummer R, Jones C, Middleton M, Wilson R, Evans J, Olsen A, et al. Phase I study of the poly(ADP-ribose) polymerase inhibitor, AG014699, in combination with temozolomide in patients with advanced solid tumors. Clin Cancer Res 2008; 14: 7917–7923
   PubMed Web of Science ®Google Scholar
• Kampinga HH. Cell biological effects of hyperthermia alone or combined with radiation or drugs: A short introduction to newcomers in the field. Int J Hyperthermia 2006; 22: 191–196
   PubMed Web of Science ®Google Scholar
• Calderwood SK, Ciocca DR. Heat shock proteins: Stress proteins with Janus-like properties in cancer. Int J Hyperthermia 2008; 24: 31–39
   PubMed Web of Science ®Google Scholar
• Mayer MP. Phosphotyrosine confers client specificity to Hsp90. Mol Cell 2010; 37: 295–296
   PubMed Web of Science ®Google Scholar
• Vaughan CK, Neckers L, Piper PW. Understanding of the Hsp90 molecular chaperone reaches new heights. Nat Struct Mol Biol 2010; 17: 1400–1404
   PubMed Web of Science ®Google Scholar
• Neckers L, Ivy SP. Heat shock protein 90. Curr Opin Oncol 2003; 15: 419–424
   PubMed Web of Science ®Google Scholar
• Calderwood SK. Heat shock proteins in breast cancer progression – A suitable case for treatment?. Int J Hyperthermia 2010; 26: 681–685
   PubMed Web of Science ®Google Scholar
• Staufer K, Stoeltzing O. Implication of heat shock protein 90 (Hsp90) in tumor angiogenesis: A molecular target for anti-angiogenic therapy?. Curr Cancer Drug Targets 2010; 10: 890–897
   PubMed Web of Science ®Google Scholar
• Trepel J, Mollapour M, Giaccone G, Neckers L. Targeting the dynamic Hsp90 complex in cancer. Nat Rev Cancer 2010; 10: 537–549
   PubMed Web of Science ®Google Scholar
• Neckers L, Workman P. Hsp90 molecular chaperone inhibitors: Are we there yet?. Clin Cancer Res 2012; 18: 64–76
   PubMed Web of Science ®Google Scholar
• Bishop SC, Burlison JA, Blagg BS. Hsp90: A novel target for the disruption of multiple signaling cascades. Curr Cancer Drug Targets 2007; 7: 369–388
   PubMed Web of Science ®Google Scholar
• Yamashita T, Oda T, Sekimoto T. Hsp90 and the Fanconi anemia pathway: A molecular link between protein quality control and the DNA damage response. Cell Cycle 2007; 6: 2232–2235
   PubMed Web of Science ®Google Scholar
• Whitesell L, Lindquist SL. Hsp90 and the chaperoning of cancer. Nat Rev Cancer 2005; 5: 761–772
   PubMed Web of Science ®Google Scholar
• Sangster TA, Queitsch C, Lindquist S. Hsp90 and chromatin: Where is the link?. Cell Cycle 2003; 2: 166–168
   PubMed Web of Science ®Google Scholar
• Russell JS, Burgan W, Oswald KA, Camphausen K, Tofilon PJ. Enhanced cell killing induced by the combination of radiation and the heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin: A multitarget approach to radiosensitization. Clin Cancer Res 2003; 9: 3749–3755
   PubMed Web of Science ®Google Scholar
• Bull EE, Dote H, Brady KJ, Burgan WE, Carter DJ, Cerra MA, et al. Enhanced tumor cell radiosensitivity and abrogation of G2 and S phase arrest by the Hsp90 inhibitor 17 -(dimethylaminoethylamino)-17-demethoxygeldanamycin. Clin Cancer Res 2004; 10: 8077–8084
   PubMed Web of Science ®Google Scholar
• Bisht KS, Bradbury CM, Mattson D, Kaushal A, Sowers A, Markovina S, et al. Geldanamycin and 17-allylamino-17-demethoxygeldanamycin potentiate the in vitro and in vivo radiation response of cervical tumor cells via the heat shock protein 90-mediated intracellular signaling and cytotoxicity. Cancer Res 2003; 63: 8984–8995
   PubMed Web of Science ®Google Scholar
• Enmon R, Yang WH, Ballangrud AM, Solit DB, Heller G, Rosen N, et al. Combination treatment with 17 -N-allylamino-17-demethoxy geldanamycin and acute irradiation produces supra-additive growth suppression in human prostate carcinoma spheroids. Cancer Res 2003; 63: 8393–8399
   PubMed Web of Science ®Google Scholar
• Harashima K, Akimoto T, Nonaka T, Tsuzuki K, Mitsuhashi N, Nakano T. Heat shock protein 90 (Hsp90) chaperone complex inhibitor, radicicol, potentiated radiation21 induced cell killing in a hormone-sensitive prostate cancer cell line through degradation of the androgen receptor. Int J Radiat Biol 2005; 81: 63–76
   PubMed Web of Science ®Google Scholar
• Machida H, Matsumoto Y, Shirai M, Kubota N. Geldanamycin, an inhibitor of Hsp90, sensitizes human tumour cells to radiation. Int J Radiat Biol 2003; 79: 973–980
   PubMed Web of Science ®Google Scholar
• Stingl L, Stuhmer T, Chatterjee M, Jensen MR, Flentje M, Djuzenova CS. Novel Hsp90 inhibitors, NVP-AUY922 and NVP-BEP800, radiosensitise tumour cells through cellcycle impairment, increased DNA damage and repair protraction. Br J Cancer 2010; 102: 1578–1591
   PubMed Web of Science ®Google Scholar
• Dote H, Burgan WE, Camphausen K, Tofilon PJ. Inhibition of hsp90 compromises the DNA damage response to radiation. Cancer Res 2006; 66: 9211–9220
   PubMed Web of Science ®Google Scholar
• Ha K, Fiskus W, Rao R, Balusu R, Venkannagari S, Nalabothula NR, et al. Hsp90 inhibitor-mediated disruption of chaperone association of ATR with Hsp90 sensitizes cancer cells to DNA damage. Mol Cancer Ther 2011; 10: 1194–1206
   PubMed Web of Science ®Google Scholar
• Oda T, Hayano T, Miyaso H, Takahashi N, Yamashita T. Hsp90 regulates the Fanconi anemia DNA damage response pathway. Blood 2007; 109: 5016–5026
   PubMed Web of Science ®Google Scholar
• Koll TT, Feis SS, Wright MH, Teniola MM, Richardson MM, Robles AI, et al. Hsp90 inhibitor, DMAG, synergizes with radiation of lung cancer cells by interfering with base excision and ATM-mediated DNA repair. Mol Cancer Ther 2008; 7: 1985–1992
   PubMed Web of Science ®Google Scholar
• Noguchi M, Yu D, Hirayama R, Ninomiya Y, Sekine E, Kubota N, et al. Inhibition of homologous recombination repair in irradiated tumor cells pretreated with Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin. Biochem Biophys Res Commun 2006; 351: 658–663
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Ito A, Saito H, Mitobe K, Minamiya Y, Takahashi N, Maruyama K, et al. Inhibition of heat shock protein 90 sensitizes melanoma cells to thermosensitive ferromagnetic particle-mediated hyperthermia with low Curie temperature. Cancer Sci 2009; 100: 558–564
   PubMed Web of Science ®Google Scholar
• van der Zee J, van Rhoon GC. Cervical cancer: Radiotherapy and hyperthermia. Int J Hyperthermia 2006; 22: 229–234
   PubMed Web of Science ®Google Scholar
• Calderwood SK, Asea A. Targeting Hsp70-induced thermotolerance for design of thermal sensitizers. Int J Hyperthermia 2002; 18: 597–608
   PubMed Web of Science ®Google Scholar
• Massey AJ, Williamson DS, Browne H, Murray JB, Dokurno P, Shaw T, et al. A novel, small molecule inhibitor of Hsc70/Hsp70 potentiates Hsp90 inhibitor induced apoptosis in HCT116 colon carcinoma cells. Cancer Chemother Pharmacol 2010; 66: 535–545
   PubMed Web of Science ®Google Scholar
• Gortzak E, Azzarelli A, Buesa J, Bramwell VH, van Coevorden F, van Geel AN, et al. A randomised phase II study on neo-adjuvant chemotherapy for ‘high-risk’ adult soft tissue sarcoma. Eur J Cancer 2001; 37: 1096–1103
   PubMed Web of Science ®Google Scholar
• Weiss C, Engehausen DG, Krause FS, Papadopoulos T, Dunst J, Sauer R, et al. Radiochemotherapy with cisplatin and 5-fluorouracil after transurethral surgery in patients with bladder cancer. Int J Radiat Oncol Biol Phys 2007; 68: 1072–1080
   PubMed Web of Science ®Google Scholar
• Franckena M, Fatehi D, de Bruijne M, Canters RA, van Norden Y, Mens JW, et al. Hyperthermia dose–effect relationship in 420 patients with cervical cancer treated with combined radiotherapy and hyperthermia. Eur J Cancer 2009; 45: 1969–1978
   PubMed Web of Science ®Google Scholar
• Ott OJ, Rodel C, Weiss C, Wittlinger M, St Krause F, Dunst J, et al. Radiochemotherapy for bladder cancer. Clin Oncol (R Coll Radiol) 2009; 21: 557–565
   PubMed Web of Science ®Google Scholar
• Issels RD, Lindner LH, Verweij J, Wust P, Reichardt P, Schem BC, et al. Neoadjuvant chemotherapy alone or with regional hyperthermia for localised high-risk soft tissue sarcoma: A randomised phase 3 multicentre study. Lancet Oncol 2010; 11: 561–570
   PubMed Web of Science ®Google Scholar
• Krause FS, Walter B, Ott OJ, Haberle L, Weiss C, Rodel C, et al. 15-year survival rates after transurethral resection and radiochemotherapy or radiation in bladder cancer treatment. Anticancer Res 2011; 31: 985–990
   PubMed Web of Science ®Google Scholar
• Issels RD. Hyperthermia adds to chemotherapy. Eur J Cancer 2008; 44: 2546–2554
   PubMed Web of Science ®Google Scholar
• Wust P, Hildebrandt B, Sreenivasa G, Rau B, Gellermann J, Riess H, et al. Hyperthermia in combined treatment of cancer. Lancet Oncol 2002; 3: 487–497
   PubMed Web of Science ®Google Scholar
• Horsman MR, Overgaard J. Hyperthermia: A potent enhancer of radiotherapy. Clin Oncol (R Coll Radiol) 2007; 19: 418–426
   PubMed Web of Science ®Google Scholar
• Treszezamsky AD, Kachnic LA, Feng Z, Zhang J, Tokadjian C, Powell SN. BRCA1-and BRCA2-deficient cells are sensitive to etoposide-induced DNA double-strand breaks via topoisomerase II. Cancer Res 2007; 67: 7078–7081
   PubMed Web of Science ®Google Scholar
• Tsaryk R, Fabian K, Thacker J, Kaina B. Xrcc2 deficiency sensitizes cells to apoptosis by MNNG and the alkylating anticancer drugs temozolomide, fotemustine and mafosfamide. Cancer Lett 2006; 239: 305–313
   PubMed Web of Science ®Google Scholar
• Nojima K, Hochegger H, Saberi A, Fukushima T, Kikuchi K, Yoshimura M, et al. Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells. Cancer Res 2005; 65: 11704–11711
   PubMed Web of Science ®Google Scholar
• Sekine-Suzuki E, Yu D, Kubota N, Okayasu R, Anzai K. Sulforaphane induces DNA double strand breaks predominantly repaired by homologous recombination pathway in human cancer cells. Biochem Biophys Res Commun 2008; 377: 341–345
   PubMed Web of Science ®Google Scholar