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Tumor Biology
Erschienen in: Tumor Biology 9/2016

19.06.2016 | Review

Emerging targets for radioprotection and radiosensitization in radiotherapy

verfasst von: Sumit Kumar, Rajnish Kumar Singh, Ramovatar Meena

Erschienen in: Tumor Biology | Ausgabe 9/2016

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Abstract

Radiotherapy is the biggest force acting behind cancer treatment, yet the vast majority of patients get only modest benefit. The successive failure of targeted therapies in radiotherapy lies in the non-discriminative killing of both normal and cancer cells. However, there is still a reason for optimism due to recent advancement made in cancer biology which unrevealed many new deregulated pathways in cancer and their response towards drug and radiation. In this review, we comprehensively discussed novel and promising druggable target which can be exploited for tumor radiosensitization in addition to normal tissue radioprotection in radiotherapy, for better tumor controllability and patient quality of life. In the last part, we also discussed the radiation countermeasure agents in brief.
Literatur
1.
Edison TA. Effect of x-rays upon the eye. Nature. 1896;53:1.
2.
Thariat J, Hannoun-Levi JM, Sun Myint A, Vuong T, Gerard JP. Past, present, and future of radiotherapy for the benefit of patients. Nat Rev Clin Oncol. 2013;10:52–60.PubMedCrossRef
3.
4.
Sansare K, Khanna V, Karjodkar F. Early victims of x-rays: a tribute and current perception. Dentomaxillofacial Radiol. 2014;40:123–5.CrossRef
5.
6.
7.
Patt HM, Tyree EB, Straube RL, Smith DE. Cysteine protection against x irradiation. Science. 1949;110:213–4.PubMedCrossRef
8.
Gray LH, Conger AD, Ebert M, Hornsey S, Scott OC. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol. 1953;26:638–48.PubMedCrossRef
9.
Åkerfeldt S, Rönnbäck C, Nelson A. Radioprotective agents: results with S-(3-amino-2-hydroxypropyl) phosphorothioate, amidophosphorothioate, and some related compounds. Radiat Res. 1967;31:850–5.CrossRef
10.
Bray F, Jemal A, Grey N, Ferlay J, Forman D. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol. 2012;13:790–801.PubMedCrossRef
11.
Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19:1893–907.PubMedCrossRef
12.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2015;66:7–30.CrossRef
13.
14.
15.
Kaplan HS. Hodgkin’s disease. Cambridge: Harvard University Press; 1980.
16.
Choi WH, Cho J. Evolving clinical cancer radiotherapy: concerns regarding normal tissue protection and quality assurance. J Korean Med Sci. 2015;30.
17.
Lattime EC, Gerson SL. Gene therapy of cancer: translational approaches from preclinical studies to clinical implementation. Amsterdam: Elsevier Science; 2013.
18.
Epperly MW, Gretton JE, Sikora CA, Jefferson M, Bernarding M, Nie S, et al. Mitochondrial localization of superoxide dismutase is required for decreasing radiation-induced cellular damage. Radiat Res. 2003;160:568–78.PubMedCrossRef
19.
Jin C, Qin L, Shi Y, Candas D, Fan M, Lu CL, et al. CDK4-mediated MnSOD activation and mitochondrial homeostasis in radioadaptive protection. Free Radicals Biol Med. 2015;81:77–87.CrossRef
20.
Miriyala S, Spasojevic I, Tovmasyan A, Salvemini D, Vujaskovic Z, St Clair D, et al. Manganese superoxide dismutase, MnSOD and its mimics. Biochim Biophys Acta, Rev Cancer. 2012;1822:794–814.CrossRef
21.
ATBC. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994;330:1029–35.CrossRef
22.
Guo L, Zhu H, Lin C, Che J, Tian X, Han S, et al. Associations between antioxidant vitamins and the risk of invasive cervical cancer in Chinese women: A case-control study. Sci Rep. 2015;5:13607.PubMedPubMedCentralCrossRef
23.
Welch RW, Turley E, Sweetman SF, Kennedy G, Collins AR, Dunne A, et al. Dietary antioxidant supplementation and DNA damage in smokers and nonsmokers. Nutr Cancer. 1999;34:167–72.PubMedCrossRef
24.
Liu Q, Jin J, Ying J, Sun M, Cui Y, Zhang L, et al. Frequent epigenetic suppression of tumor suppressor gene glutathione peroxidase 3 by promoter hypermethylation and its clinical implication in clear cell renal cell carcinoma. Int J Mol Sci. 2015;16:10636–49.PubMedPubMedCentralCrossRef
25.
Trachootham D, Alexandre J, Huang P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discovery. 2009;8:579–91.PubMedCrossRef
26.
Tarhini AA, Belani CP, Luketich JD, Argiris A, Ramalingam SS, Gooding W, et al. A phase I study of concurrent chemotherapy (paclitaxel and carboplatin) and thoracic radiotherapy with swallowed manganese superoxide dismutase plasmid liposome protection in patients with locally advanced stage III non-small-cell lung cancer. Hum Gene Ther. 2011;22:336–42.PubMedCrossRef
27.
Colon J, Hsieh N, Ferguson A, Kupelian P, Seal S, Jenkins DW, et al. Cerium oxide nanoparticles protect gastrointestinal epithelium from radiation-induced damage by reduction of reactive oxygen species and upregulation of superoxide dismutase 2. Nanomedicine. 2010;6:698–705.PubMed
28.
Wason MS, Colon J, Das S, Seal S, Turkson J, Zhao J, et al. Sensitization of pancreatic cancer cells to radiation by cerium oxide nanoparticle-induced ROS production. Nanomedicine. 2013;9:558–69.PubMed
29.
Asati A, Santra S, Kaittanis C, Perez JM. Surface-charge-dependent cell localization and cytotoxicity of cerium oxide nanoparticles. ACS Nano. 2010;4:5321–31.PubMedPubMedCentralCrossRef
30.
Johnke RM, Sattler JA, Allison RR. Radioprotective agents for radiation therapy: future trends. Future Oncol. 2014;10:2345–57.PubMedCrossRef
31.
Epperly MW, Shinde A, Berhane H, Rhieu BH, Kalash R, Xu K, et al. Abstract 3340: Intraoral administration of mitochondrial targeted GS-nitroxide (JP4-039) radioprotects the oral mucosa but not orthotopic tumors in Fancd2-/- mice. Cancer Res. 2015;75:3340.CrossRef
32.
Metz JM, Smith D, Mick R, Lustig R, Mitchell J, Cherakuri M, et al. A phase I study of topical Tempol for the prevention of alopecia induced by whole brain radiotherapy. Clin Cancer Res. 2004;10:6411–7.PubMedCrossRef
33.
Erker L, Schubert R, Yakushiji H, Barlow C, Larson D, Mitchell JB, et al. Cancer chemoprevention by the antioxidant tempol acts partially via the p53 tumor suppressor. Hum Mol Genet. 2005;14(12):1699–708.PubMedCrossRef
34.
Mihandoost E, Shirazi A, Mahdavi SR, Aliasgharzadeh A. Can melatonin help us in radiation oncology treatments? BioMed Res Int. 2014;2014:12.CrossRef
35.
Vijayalaxmi, Reiter RJ, Tan DX, Herman TS, Thomas Jr CR. Melatonin as a radioprotective agent: a review. Int J Radiat Oncol Biol Phys. 2004;59:639–53.PubMedCrossRef
36.
Lissoni P, Meregalli S, Nosetto L, Barni S, Tancini G, Fossati V, et al. Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology. 1996;53:43–6.PubMedCrossRef
37.
Berk L, Berkey B, Rich T, Hrushesky W, Blask D, Gallagher M, et al. Randomized phase II trial of high-dose melatonin and radiation therapy for RPA class 2 patients with brain metastases (RTOG 0119). Int J Radiat Oncol Biol Phys. 2007;68:852–7.PubMedPubMedCentralCrossRef
38.
Son T, Gong E, Bae M, Kim S, Heo K, Moon C, et al. Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice. BMC Complementary Altern Med. 2013;13:103.CrossRef
39.
Kepley C, Dellinger A. Fullerenes and their potential in nanomedicine in book Nanoscience and Nanoengineering: Advances and Applications. Abingdon: Taylor & Francis; 2014.
40.
Son Y, Lee H, Rho J, Chung S, Lee C, Yang K, et al. The ameliorative effect of silibinin against radiation-induced lung injury: protection of normal tissue without decreasing therapeutic efficacy in lung cancer. BMC Pulm Med. 2015;15:68.PubMedPubMedCentralCrossRef
41.
Albright CD, Salganik RI, Van Dyke T. Dietary depletion of vitamin E and vitamin A inhibits mammary tumor growth and metastasis in transgenic mice. J Nutr. 2004;134:1139–44.PubMed
42.
Salganik RI, Albright CD, Rodgers J, Kim J, Zeisel SH, Sivashinskiy MS, et al. Dietary antioxidant depletion: enhancement of tumor apoptosis and inhibition of brain tumor growth in transgenic mice. Carcinogenesis. 2000;21:909–14.PubMedCrossRef
43.
Sayin VI, Ibrahim MX, Larsson E, Nilsson JA, Lindah lP, Bergo MO. Antioxidants accelerate lung cancer progression in mice. Sci Transl Med. 2014;6:221ra215.CrossRef
44.
Lawenda BD, Kelly KM, Ladas EJ, Sagar SM, Vickers A, Blumberg JB. Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer Inst. 2008;100:773–83.PubMedCrossRef
45.
Braunstein MH. Vitamin E: new research. New York: Nova Science Publishers; 2006.
46.
Lesperance ML, Olivotto IA, Forde N, Zhao Y, Speers C, Foster H, et al. Mega-dose vitamins and minerals in the treatment of non-metastatic breast cancer: an historical cohort study. Breast Cancer Res Treat. 2002;76:137–43.PubMedCrossRef
47.
Misirlioglu CH, Demirkasimoglu T, Kucukplakci B, Sanri E, Altundag K. Pentoxifylline and alpha-tocopherol in prevention of radiation-induced lung toxicity in patients with lung cancer. Med Oncol. 2007;24:308–11.PubMedCrossRef
48.
Misirlioglu CH, Erkal H, Elgin Y, Ugur I, Altundag K. Effect of concomitant use of pentoxifylline and alpha-tocopherol with radiotherapy on the clinical outcome of patients with stage IIIB non-small cell lung cancer: a randomized prospective clinical trial. Med Oncol. 2006;23:185–9.PubMedCrossRef
49.
Borek C. Antioxidants and radiation therapy. J of Nutr. 2004;134:3207S–9.
50.
Zhao H, Zhu W, Xie P, Li H, Zhang X, et al. A phase I study of concurrent chemotherapy and thoracic radiotherapy with oral epigallocatechin-3-gallate protection in patients with locally advanced stage III non-small-cell lung cancer. Radiother Oncol. 2014;110:132–6.PubMedCrossRef
51.
Jacobson G, Bhatia S, Smith BJ, Button AM, Bodeker K, Buatti J. Randomized trial of pentoxifylline and vitamin E vs standard follow-up after breast irradiation to prevent breast fibrosis, evaluated by tissue compliance meter. Int J Radiat Oncol Biol Phys. 2013;85:604–8.PubMedCrossRef
52.
Zhao H, Xie P, Li X, Zhu W, Sun X, Chen X, et al. A prospective phase II trial of EGCG in treatment of acute radiation-induced esophagitis for stage III lung cancer. Radiother Oncol. 2015;114:351–6.PubMedCrossRef
53.
Feng M, Smith DE, Normolle DP, Knol JA, Pan CC, Ben-Josef E, et al. A phase I clinical and pharmacology study using amifostine as a radioprotector in dose-escalated whole liver radiation therapy. Int J Radiat Oncol Biol Phys. 2012;83:1441–7.PubMedPubMedCentralCrossRef
54.
Panteliadou M, Giatromanolaki A, Touloupidis S, Destouni E, Tsoutsou PG, Pantelis P, et al. Treatment of invasive bladder cancer with conformal hypofractionated accelerated radiotherapy and amifostine (HypoARC). Urol Oncol. 2012;30:813–20.PubMedCrossRef
55.
Lawrence YR, Paulus R, Langer C, Werner-Wasik M, Buyyounouski MK, Komaki R, et al. The addition of amifostine to carboplatin and paclitaxel based chemoradiation in locally advanced non-small cell lung cancer: long- term follow-up of Radiation Therapy Oncology Group (RTOG) randomized trial 9801. Lung Cancer. 2013;80:298–305.PubMedCrossRef
56.
Gu J, Zhu S, Li X, Wu H, Li Y, Hua F. Effect of amifostine in head and neck cancer patients treated with radiotherapy: a systematic review and meta-analysis based on randomized controlled trials. PLoS One. 2014;9:e95968.PubMedPubMedCentralCrossRef
57.
Movsas B, Scott C, Langer C, Werner-Wasik M, Nicolaou N, Komaki R, et al. Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98-01. J Clin Oncol. 2005;23:2145–54.PubMedCrossRef
58.
Small Jr W, Winter K, Levenback C, Iyer R, Hymes SR, Jhingran A, et al. Extended-field irradiation and intracavitary brachytherapy combined with cisplatin and amifostine for cervical cancer with positive para-aortic or high common iliac lymph nodes: results of arm II of Radiation Therapy Oncology Group (RTOG) 0116. Int J Gynecol Cancer. 2011;21:1266–75.PubMedCrossRef
59.
Koukourakis MI. Amifostine: is there evidence of tumor protection? Semin Oncol. 2003;30(6 Suppl 18):18–30.PubMedCrossRef
60.
Rades D, Fehlauer F, Bajrovic A, Mahlmann B, Richter E, Alberti W. Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients. Radiother Oncol. 2004;70:261–4.PubMedCrossRef
61.
Grdina DJ, Murley JS, Kataoka Y, Baker KL, Kunnavakkam R, Coleman MC, et al. Amifostine induces antioxidant enzymatic activities in normal tissues and a transplantable tumor that can affect radiation response. Int J Radiat Oncol Biol Phys. 2009;73:886–96.PubMedPubMedCentralCrossRef
62.
Thomas JP, Geiger PG. Abstract 4443: PB-42: design and characterization of a glutathione pro-drug selectively delivered to normal tissue and not tumor tissue. Cancer Res. 2015;75:4443.CrossRef
63.
Cerutti P. Anticarcinogenesis and radiation protection. New York, Philadelphia: Springer; 2012.
64.
Lu SC. Glutathione synthesis. Biochim Biophys Acta. 1830;2013:3143–53.
65.
Zhang WC, Shyh-Chang N, Yang H, Rai A, Umashankar S, Ma S, et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell. 2012;148:259–72.PubMedCrossRef
66.
Shaul YD, Freinkman E, Comb WC, Cantor JR, Tam WL, Thiru P, et al. Dihydropyrimidine accumulation is required for the epithelial-mesenchymal transition. Cell. 2014;158:1094–109.PubMedPubMedCentralCrossRef
67.
Zamani Z, Arjmand M, Vahabi F, Eshaq Hosseini SM, Fazeli SM, Iravani A, et al. A metabolic study on colon cancer using 1H nuclear magnetic resonance spectroscopy. Biochem Res Int. 2014;2014:7.CrossRef
68.
Taniguchi CM, Miao YR, Diep AN, Wu C, Rankin EB, Atwood TF, et al. PHD inhibition mitigates and protects against radiation-induced gastrointestinal toxicity via HIF2. Sci Transl Med. 2014;6:236ra264.CrossRef
69.
Lagadec C, Dekmezian C, Bauche L, Pajonk F. Oxygen levels do not determine radiation survival of breast cancer stem cells. PLoS One. 2012;7:e34545.PubMedPubMedCentralCrossRef
70.
Zhong R, Xu H, Chen G, Zhao G, Gao Y, Liu X, et al. The role of hypoxia-inducible factor-1alpha in radiation induced autophagic cell death in breast cancer cells. Tumor Biol. 2015;36:7077–83.CrossRef
71.
Li CY, Li F, Sonveaux P, Dewhirst MW. Inhibition of HIF-1 activation for anti-tumor and anti-inflammatory responses. Google Patents. 2015.
72.
Urtasun RC, Chapman JD, Feldstein ML, Band RP, Rabin HR, Wilson AF, et al. Peripheral neuropathy related to misonidazole: incidence and pathology. Br J Cancer Suppl. 1978;3:271–5.PubMedPubMedCentral
73.
Overgaard J, Hansen HS, Overgaard M, Bastholt L, Berthelsen A, Specht L, et al. A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85. Radiother Oncol. 1998;46:135–46.PubMedCrossRef
74.
Zeman EM, Brown JM, Lemmon MJ, Hirst VK, Lee WW. SR-4233: a new bioreductive agent with high selective toxicity for hypoxic mammalian cells. Int J Radiat Oncol Biol Phys. 1986;12:1239–42.PubMedCrossRef
75.
Yeh JJ, Kim WY. Targeting tumor hypoxia with hypoxia-activated prodrugs. J Clin Oncol. 2015;33:1505–8.PubMedCrossRef
76.
DiSilvestro PA, Ali S, Craighead PS, Lucci JA, Lee YC, Cohn DE, et al. Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study. J Clin Oncol. 2014;32:458–64.PubMedPubMedCentralCrossRef
77.
Toustrup K, Sorensen BS, Lassen P, Wiuf C, Alsner J, Overgaard J. Gene expression classifier predicts for hypoxic modification of radiotherapy with nimorazole in squamous cell carcinomas of the head and neck. Radiother Oncol. 2012;102:122–9.PubMedCrossRef
78.
Yoon C, Lee HJ, Park DJ, Lee YJ, Tap WD, Eisinger-Mathason TSK, et al. Hypoxia-activated chemotherapeutic TH-302 enhances the effects of VEGF-A inhibition and radiation on sarcomas. Br J Cancer. 2015;113:46–56.PubMedPubMedCentralCrossRef
79.
Sun JD, Ahluwalia D, Liu Q, Li W, Wang Y, Meng F, et al. Combination treatment with hypoxia-activated prodrug evofosfamide (TH-302) and mTOR inhibitors results in enhanced antitumor efficacy in preclinical renal cell carcinoma models. Am J Cancer Res. 2015;5:2139–55.PubMedPubMedCentral
80.
Peeters SGJA, Zegers CML, Biemans R, Lieuwes NG, van Stiphout RGPM, Yaromina A, et al. TH-302 in combination with radiotherapy enhances the therapeutic outcome and is associated with pretreatment [18F]HX4 hypoxia PET imaging. Clin Cancer Res. 2015;21:2984–92.PubMedCrossRef
81.
Chawla SP, Cranmer LD, Van Tine BA, Reed DR, Okuno SH, Butrynski JE, et al. Phase II study of the safety and antitumor activity of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma. J Clin Oncol. 2014;32:3299–306.PubMedPubMedCentralCrossRef
82.
Fahl WE. Effect of topical vasoconstrictor exposure upon tumoricidal radiotherapy. Int J Cancer. 2014;135:981–8.PubMedCrossRef
83.
Scicinski J, Oronsky B, Ning S, Knox S, Peehl D, Kim MM, et al. NO to cancer: the complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001. Redox Biol. 2015;6:1–8.PubMedPubMedCentralCrossRef
84.
Higgins GS, O’Cathail SM, Muschel RJ, McKenna WG. Drug radiotherapy combinations: review of previous failures and reasons for future optimism. Cancer Treat Rev. 2015;41:105–113.
85.
Zannella VE, Dal Pra A, Muaddi H, McKee TD, Stapleton S, Sykes J, et al. Reprogramming metabolism with metformin improves tumor oxygenation and radiotherapy response. Clin Cancer Res. 2013;19:6741–50.PubMedCrossRef
86.
Chen YC, Kok VC, Chien CH, Horng JT, Tsai JJ. Cancer risk in patients aged 30 years and above with type 2 diabetes receiving antidiabetic monotherapy: a cohort study using metformin as the comparator. Ther Clin Risk Manag. 2015;11:1315–23.PubMedPubMedCentral
87.
Liebmann J, DeLuca AM, Coffin D, Keefer LK, Venzon D, Wink DA, et al. In vivo radiation protection by nitric oxide modulation. Cancer Res. 1994;54:3365–8.PubMed
88.
Maxhimer JB, Soto-Pantoja DR, Ridnour LA, Shih HB, Degraff WG, Tsokos M, et al. Radioprotection in normal tissue and delayed tumor growth by blockade of CD47 signaling. Sci Transl Med. 2009;1:3ra7.PubMedPubMedCentralCrossRef
89.
Soto-Pantoja DR, Miller TW, Pendrak ML, DeGraff WG, Sullivan C, Ridnour LA, et al. CD47 deficiency confers cell and tissue radioprotection by activation of autophagy. Autophagy. 2012;8:1628–42.PubMedPubMedCentralCrossRef
90.
Fens MH, Larkin SK, Oronsky B, Scicinski J, Morris CR, Kuypers FA. The capacity of red blood cells to reduce nitrite determines nitric oxide generation under hypoxic conditions. PLoS One. 2014;9:e101626.PubMedPubMedCentralCrossRef
91.
Verhagen CVM, de Haan R, Hageman F, Oostendorp TPD, Carli ALE, O’Connor MJ, 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;116:358–65.PubMedCrossRef
92.
Alagpulinsa D, Ayyadevara S, Yaccoby S, Shmookler Reis R. Dinaciclib, a CDK inhibitor, impairs homologous recombination and sensitizes multiple myeloma cells to PARP inhibition. Blood. 2014;124:479.CrossRef
93.
Liu X, Cotrim A, Teos L, Zheng C, Swaim W, Mitchell J, et al. Loss of TRPM2 function protects against irradiation-induced salivary gland dysfunction. Nat Commun. 2013;4:1515.PubMedPubMedCentralCrossRef
94.
Nowacka-Zawisza M, Wiśnik E, Wasilewski A, Skowrońska M, Forma E, Bryś M, et al. Polymorphisms of homologous recombination RAD51, RAD51B, XRCC2, and XRCC3 genes and the risk of prostate cancer. Anal Cell Pathol. 2015;2015:9.CrossRef
95.
Mohaghegh P, Hickson ID. DNA helicase deficiencies associated with cancer predisposition and premature ageing disorders. Hum Mol Genet. 2001;10:741–6.PubMedCrossRef
96.
Cerbinskaite A, Mukhopadhyay A, Plummer ER, Curtin NJ, Edmondson RJ. Defective homologous recombination in human cancers. Cancer Treat Rev. 2012;38:89–100.PubMedCrossRef
97.
Su Y, Meador JA, Calaf GM, De-Santis LP, Zhao Y, Bohr VA, et al. Human RecQL4 helicase plays critical roles in prostate carcinogenesis. Cancer Res. 2010;70:9207–17.PubMedPubMedCentralCrossRef
98.
Koppensteiner R, Samartzis EP, Noske A, von Teichman A, Dedes I, Gwerder M, et al. Effect of MRE11 loss on PARP-inhibitor sensitivity in endometrial cancer in vitro. PLoS One. 2014;9:e100041.PubMedPubMedCentralCrossRef
99.
Bartosova Z, Krejci L. Nucleases in homologous recombination as targets for cancer therapy. FEBS Lett. 2014;588:2446–56.PubMedCrossRef
100.
Helleday T. Homologous recombination in cancer development, treatment and development of drug resistance. Carcinogenesis. 2010;31:955–60.PubMedCrossRef
101.
Castri P, Lee YJ, Ponzio T, Maric D, Spatz M, Bembry J, et al. Poly(ADP-ribose) polymerase-1 and its cleavage products differentially modulate cellular protection through NF-kappaB-dependent signaling. Biochim Biophys Acta, Mol Cell Res. 2014;1843:640–51.PubMedPubMedCentralCrossRef
102.
Nagasawa H, Li CY, Maki CG, Imrich AC, Little JB. Relationship between radiation-induced G1 phase arrest and p53 function in human tumor cells. Cancer Res. 1995;55:1842–6.PubMed
103.
Bridges KA, Hirai H, Buser CA, Brooks C, Liu H, Buchholz TA, et al. MK-1775, a novel Wee1 kinase inhibitor, radiosensitizes p53-defective human tumor cells. Clin Cancer Res. 2011;17:5638–48.PubMedPubMedCentralCrossRef
104.
Pappano W, Zhang Q, Tucker L, Tse C, Wang J. Genetic inhibition of the atypical kinase Wee1 selectively drives apoptosis of p53 inactive tumor cells. BMC Cancer. 2014;14:430.PubMedPubMedCentralCrossRef
105.
Leijen S, Beijnen JH, Schellens JH. Abrogation of the G2 checkpoint by inhibition of Wee-1 kinase results in sensitization of p53-deficient tumor cells to DNA-damaging agents. Curr Clin Pharmacol. 2010;5:186–91.PubMedCrossRef
106.
107.
Fokas E, Prevo R, Hammond EM, Brunner TB, McKenna WG, Muschel RJ. Targeting ATR in DNA damage response and cancer therapeutics. Cancer Treat Rev. 2014;40:109–17.PubMedCrossRef
108.
Brown EJ, Baltimore D. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 2000;14:397–402.PubMedPubMedCentral
109.
Murga M, Bunting S, Montana MF, Soria R, Mulero F, Canamero M, et al. A mouse model of ATR-Seckel shows embryonic replicative stress and accelerated aging. Nat Genet. 2009;41:891–8.PubMedPubMedCentralCrossRef
110.
Ruzankina Y, Schoppy DW, Asare A, Clark CE, Vonderheide RH, Brown EJ. Tissue regenerative delays and synthetic lethality in adult mice after combined deletion of Atr and Trp53. Nat Genet. 2009;41:1144–9.PubMedPubMedCentralCrossRef
111.
Reaper PM, Griffiths MR, Long JM, Charrier JD, Maccormick S, Charlton PA. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol. 2011;7:428–430.
112.
Fujisawa H, Nakajima NI, Sunada S, Lee Y, Hirakawa H, Yajima H, et al. VE-821, an ATR inhibitor, causes radiosensitization in human tumor cells irradiated with high LET radiation. Radiat Oncol. 2015;10:175.PubMedPubMedCentralCrossRef
113.
Fokas E, Prevo R, Pollard JR, Reaper PM, Charlton PA, Cornelissen B, et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012;3:e441.PubMedPubMedCentralCrossRef
114.
Foote KM, Blades K, Cronin A, Fillery S, Guichard SS, Hassall L, et al. Discovery of 4-{4-[(3R)-3 Methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-y l}-1H-indole (AZ20): a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity. J Med Chem. 2013;56:2125–38.PubMedCrossRef
115.
Kwok M, Davies N, Agathanggelou A, Smith E, Oldreive C, Petermann E, et al. ATR inhibition induces synthetic lethality and overcomes chemoresistance in TP53 or ATM defective chronic lymphocytic leukemia cells. Blood. 2015.
116.
Sarkaria JN, Busby EC, Tibbetts RS, Roos P, Taya Y, Karnitz LM, et al. Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Res. 1999;59:4375–82.PubMed
117.
Sultana R, Abdel-Fatah T, Perry C, Moseley P, Albarakti N, Mohan V, et al. Ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase inhibition is synthetically lethal in XRCC1 deficient ovarian cancer cells. PLoS One. 2013;8:e57098.PubMedPubMedCentralCrossRef
118.
Weber AM, Ryan AJ. ATM and ATR as therapeutic targets in cancer. Pharmacol Ther. 2015;149:124–38.PubMedCrossRef
119.
Beumer JH, Fu KY, Anyang BN, Siegfried JM, Bakkenist CJ. Functional analyses of ATM, ATR and Fanconi anemia proteins in lung carcinoma : ATM, ATR and FA in lung carcinoma. BMC cancer. 2015;15:1–10.
120.
Beumer JH, Fu KY, Anyang BN, Siegfried JM, Bakkenist CJ. Functional analyses of ATM, ATR and Fanconi anemia proteins in lung carcinoma. BMC Cancer. 2015;15:1–10.CrossRef
121.
Zhang T, Shen Y, Chen Y, Hsieh JT, Kong Z. The ATM inhibitor KU55933 sensitizes radioresistant bladder cancer cells with DAB2IP gene defect. Int J Radiat Biol. 2015;91:368–78.PubMedCrossRef
122.
Teng P, Bateman NW, Darcy KM, Hamilton CA, Maxwell GL, Bakkenist CJ. Pharmacologic inhibition of ATR and ATM offers clinically important distinctions to enhancing platinum or radiation response in ovarian, endometrial, and cervical cancer cells. Gynecol Oncol. 2015;136:554–61.PubMedPubMedCentralCrossRef
123.
Carruthers R, Ahmed SU, Strathdee K, Gomez-Roman N, Amoah-Buahin E, Watts C, et al. Abrogation of radioresistance in glioblastoma stem-like cells by inhibition of ATM kinase. Mol Oncol. 2015;9:192–203.PubMedCrossRef
124.
Choi S, Gamper AM, White JS, Bakkenist CJ. Inhibition of ATM kinase activity does not phenocopy ATM protein disruption: implications for the clinical utility of ATM kinase inhibitors. Cell Cycle. 2010;9:4052–7.PubMedPubMedCentralCrossRef
125.
White JS, Choi S, Bakkenist CJ. Transient ATM kinase inhibition disrupts DNA damage-induced sister chromatid exchange. Sci Signaling. 2010;3:ra44.CrossRef
126.
Yamamoto K, Wang Y, Jiang W, Liu X, Dubois RL, Lin CS, et al. Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice. J Cell Biol. 2012;198:305–13.PubMedPubMedCentralCrossRef
127.
Batey MA, Zhao Y, Kyle S, Richardson C, Slade A, Martin NMB, et al. Preclinical evaluation of a novel ATM inhibitor, KU59403, in vitro and in vivo in p53 functional and dysfunctional models of human cancer. Mol Cancer Ther. 2013;12:959–67.PubMedPubMedCentralCrossRef
128.
You Z, Chahwan C, Bailis J, Hunter T, Russell P. ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1. Mol Cell Biol. 2005;25:5363–79.PubMedPubMedCentralCrossRef
129.
Liao Y, Feng Y, Shen J, Hornicek F, Duan Z. The roles and therapeutic potential of cyclin-dependent kinases (CDKs) in sarcoma. Cancer Metastasis Rev. 2015;35:1-13.
130.
Barton KL, Misuraca K, Cordero F, Dobrikova E, Min HD, Gromeier M, et al. PD-0332991, a CDK4/6 inhibitor, significantly prolongs survival in a genetically engineered mouse model of brainstem glioma. PLoS One. 2013;8:e77639.PubMedPubMedCentralCrossRef
131.
Johnson SM, Torrice CD, Bell JF, Monahan KB, Jiang Q, Wang Y, et al. Mitigation of hematologic radiation toxicity in mice through pharmacological quiescence induced by CDK4/6 inhibition. J Clin Invest. 2010;120:2528–36.PubMedPubMedCentralCrossRef
132.
Roberts PJ, Bisi JE, Strum JC, Combest AJ, Darr DB, Usary JE, et al. Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy. J Natl Cancer Inst. 2012;11:3913.
133.
Indovina P, Pentimalli F, Casini N, Vocca I, Giordano A. RB1 dual role in proliferation and apoptosis: cell fate control and implications for cancer therapy. Oncotarget. 2015;6:17873–90.PubMedPubMedCentralCrossRef
134.
Hsu FT, Chang B, Chen JCH, Chiang IT, Liu YC, Kwang WK, et al. Synergistic effect of sorafenib and radiation on human oral carcinoma in vivo. Sci Rep. 2015;5:15391.PubMedPubMedCentralCrossRef
135.
Komarova EA, Chernov MV, Franks R, Wang K, Armin G, Zelnick CR, et al. Transgenic mice with p53 responsive lacZ: p53 activity varies dramatically during normal development and determines radiation and drug sensitivity in vivo. EMBO J. 1997;16:1391–400.PubMedPubMedCentralCrossRef
136.
Morita A, Ariyasu S, Wang B, Asanuma T, Onoda T, Sawa A, et al. AS-2, a novel inhibitor of p53-dependent apoptosis, prevents apoptotic mitochondrial dysfunction in a transcription-independent manner and protects mice from a lethal dose of ionizing radiation. Biochem Biophys Res Commun. 2014;450:1498–504.PubMedCrossRef
137.
Vavrova J, Rezacova M. Importance of proapoptotic protein PUMA in cell radioresistance. Folia Biol. 2014;60:53–6.
138.
Lee CL, Blum JM, Kirsch DG. Role of p53 in regulating tissue response to radiation by mechanisms independent of apoptosis. Transl Cancer Res. 2013;2:412–21.PubMedPubMedCentral
139.
Roberts M, Saffie R, Salmons H, Ghoto M, Schneider J, Forrester J. Abstract 346: differentiation induced apoptosis in AML cells: the role of p73 in p53-independent versus p53-mediated apoptosis. Cancer Res. 2014;74:346.CrossRef
140.
141.
Yu H, Shen H, Yuan Y, XuFeng R, Hu X, Garrison SP, et al. Deletion of Puma protects hematopoietic stem cells and confers long-term survival in response to high-dose gamma-irradiation. Blood. 2010;115:3472–80.PubMedPubMedCentralCrossRef
142.
Komarova EA, Kondratov RV, Wang K, Christov K, Golovkina TV, Goldblum JR, et al. Dual effect of p53 on radiation sensitivity in vivo: p53 promotes hematopoietic injury, but protects from gastro-intestinal syndrome in mice. Oncogene. 2004;23:3265–71.PubMedCrossRef
143.
Rotolo J, Stancevic B, Zhang J, Hua G, Fuller J, Yin X, et al. Anti-ceramide antibody prevents the radiation gastrointestinal syndrome in mice. J Clin Invest. 2012;122:1786–90.PubMedPubMedCentralCrossRef
144.
Greene-Schloesser D, Payne V, Peiffer AM, Hsu FC, Riddle DR, Zhao W, et al. The peroxisomal proliferator activated receptor (PPAR) α agonist, fenofibrate, prevents fractionated whole-brain irradiation-induced cognitive impairment. Radiat Res. 2014;181:33–44.PubMedPubMedCentralCrossRef
145.
Ramanan S, Kooshki M, Zhao W, Hsu FC, Riddle DR, Robbins ME. The PPARalpha agonist fenofibrate preserves hippocampal neurogenesis and inhibits microglial activation after whole-brain irradiation. Int J Radiat Oncol Biol Phys. 2009;75:870–7.PubMedPubMedCentralCrossRef
146.
Mangoni M, Sottili M, Gerini C, Bonomo P, Bottoncetti A, Castiglione F, et al. A PPAR-gamma agonist attenuates pulmonary injury induced by irradiation in a murine model. Lung Cancer. 2015;90:405–9.PubMedCrossRef
147.
Epperly MW, Melendez JA, Zhang X, Nie S, Pearce L, Peterson J, et al. Mitochondrial targeting of a catalase transgene product by plasmid liposomes increases radioresistance in vitro and in vivo. Radiat Res. 2009;171:588–95.PubMedPubMedCentralCrossRef
148.
Bechtel W, Bauer G. Catalase protects tumor cells from apoptosis induction by intercellular ROS signaling. Anticancer Res. 2009;29:4541–57.PubMed
149.
Khoo NK, Hebbar S, Zhao W, Moore SA, Domann FE, Robbins ME. Differential activation of catalase expression and activity by PPAR agonists: implications for astrocyte protection in anti-glioma therapy. Redox Biol. 2013;1:70–9.PubMedPubMedCentralCrossRef
150.
Slone HB, Peters LJ, Milas L. Effect of host immune capability on radiocurability and subsequent transplantability of a murine fibrosarcoma. J Natl Cancer Inst. 1979;63:1229–35.
151.
152.
Ruocco MG, Pilones KA, Kawashima N, Cammer M, Huang J, Babb JS, et al. Suppressing T cell motility induced by anti–CTLA-4 monotherapy improves antitumor effects. J Clin Invest. 2012;122:3718–30.PubMedPubMedCentralCrossRef
153.
Madureira P, de Mello RA, de Vasconcelos A, Zhang Y. Immunotherapy for lung cancer: for whom the bell tolls? Tumor Biol. 2015;36:1411–22.CrossRef
154.
Slovin SF, Higano CS, Hamid O, Tejwani S, Harzstark A, Alumkal JJ, et al. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann Oncol. 2013;24:1813–21.PubMedPubMedCentralCrossRef
155.
Robert C, Ribas A, Wolchok JD, Hodi FS, Hamid O, Kefford R, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet. 2014;384:1109–17.PubMedCrossRef
156.
Schaue D, McBride WH. Opportunities and challenges of radiotherapy for treating cancer. Nat Rev Clin Oncol. 2015;12:527–40.
157.
Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373:23–34.PubMedCrossRef
158.
Zeng J, See AP, Phallen J, Jackson CM, Belcaid Z, Ruzevick J, et al. Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys. 2013;86:343–9.PubMedPubMedCentralCrossRef
159.
Sharabi AB, Nirschl CJ, Kochel CM, Nirschl TR, Francica BJ, Velarde E, et al. Stereotactic radiation therapy augments antigen-specific PD-1-mediated antitumor immune responses via cross-presentation of tumor antigen. Cancer Immunol Res. 2015;3:345–55.PubMedCrossRef
160.
Dovedi SJ, Adlard AL, Lipowska-Bhalla G, McKenna C, Jones S, Cheadle EJ, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014;74:5458–68.PubMedCrossRef
161.
Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR, et al. Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014;124:687–95.PubMedPubMedCentralCrossRef
162.
Chow LQ. Exploring novel immune-related toxicities and endpoints with immune-checkpoint inhibitors in non small cell lung cancer. Am Soc Clin Oncol Educ Book. Meeting. 2013;1:280–285.
163.
Zhang D, Chen Z, Wang D, Wang X. Regulatory T cells and potential inmmunotherapeutic targets in lung cancer. Cancer Metastasis Rev. 2015;34:277–90.PubMedCrossRef
164.
Yazdani Y, Mohammadnia-Afrouzi M, Yousefi M, Anvari E, Ghalamfarsa G, et al. Myeloid-derived suppressor cells in B cell malignancies. Tumor Biol. 2015;36:7339–53.CrossRef
165.
Hu H, Hang JJ, Han T, Zhuo M, Jiao F, Wang LW. 2016. The M2 phenotype of tumor-associated macrophages in the stroma confers a poor prognosis in pancreatic cancer. Tumor biol. 2016. doi:10.​1007/​s13277-015-4741-z.
166.
Farrell CL, Bready JV, Rex KL, Chen JN, DiPalma CR, Whitcomb KL, et al. Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality. Cancer Res. 1998;58:933–9.PubMed
167.
Chen L, Brizel DM, Rabbani ZN, Samulski TV, Farrell CL, Larrier N, et al. The protective effect of recombinant human keratinocyte growth factor on radiation-induced pulmonary toxicity in rats. Int J Radiat Oncol Biol Phys. 2004;60:1520–9.PubMedCrossRef
168.
Hensley ML, Hagerty KL, Kewalramani T, Green DM, Meropol NJ, Wasserman TH, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. J Clin Oncol. 2009;27:127–45.PubMedCrossRef
169.
Henke M, Alfonsi M, Foa P, Giralt J, Bardet E, Cerezo L, et al. Palifermin decreases severe oral mucositis of patients undergoing postoperative radiochemotherapy for head and neck cancer: a randomized, placebo-controlled trial. J Clin Oncol. 2011;29:2815–20.PubMedCrossRef
170.
Le QT, Kim HE, Schneider CJ, Murakozy G, Skladowski K, Reinisch S, et al. Palifermin reduces severe mucositis in definitive chemoradiotherapy of locally advanced head and neck cancer: a randomized, placebo controlled study. J Clin Oncol. 2011;29:2808–14.PubMedCrossRef
171.
Schuette W, Krzakowski MJ, Massuti B, Otterson GA, Lizambri R, Wei H, et al. Randomized phase II study of palifermin for reducing dysphagia in patients receiving concurrent chemoradiotherapy for locally advanced unresectable non-small cell lung cancer. J Thorac Oncol. 2012;7:157–64.PubMedPubMedCentralCrossRef
172.
Vitale KM, Violago L, Cofnas P, Bishop J, Jin Z, Bhatia M, et al. Impact of palifermin on incidence of oral mucositis and healthcare utilization in children undergoing autologous hematopoietic stem cell transplantation for malignant diseases. Pediatr Transplant. 2014;18:211–6.PubMedCrossRef
173.
Ryu JK, Swann S, LeVeque F, Scarantino CW, Johnson D, Chen A, et al. The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients: a double blind placebo-controlled prospective phase III study by Radiation Therapy Oncology Group 9901. Int J Radiat Oncol Biol Phys. 2007;67:643–50.PubMedCrossRef
174.
Hoffman KE, Pugh SL, James JL, Scarantino C, Movsas B, Valicenti RK, et al. The impact of concurrent granulocyte-macrophage colony-stimulating factor on quality of life in head and neck cancer patients: results of the randomized, placebo-controlled Radiation Therapy Oncology Group 9901 trial. Qual Life Res. 2014;23:1841–58.PubMedPubMedCentralCrossRef
175.
Masucci G, Broman P, Kelly C, Lindahl S, Malmberg L, Reizenstein J, et al. Therapeutic efficacy by recombinant human granulocyte/monocyte-colony stimulating factor on mucositis occurring in patients with oral and oropharynx tumors treated with curative radiotherapy: a multicenter open randomized phase III study. Med Oncol. 2005;22:247–56.PubMedCrossRef
176.
Harrington KJ, Hingorani M, Tanay MA, Hickey J, Bhide SA, Clarke PM, et al. Phase I/II study of oncolytic HSVGM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clin Cancer Res. 2010;16:4005–15.PubMedCrossRef
177.
Lövey J, Bereczky B, Gilly R, Kenessey I, Rásó E, Simon E, et al. Recombinant human erythropoietin alpha improves the efficacy of radiotherapy of a human tumor xenograft, affecting tumor cells and microvessels. Strahlenther Onkol. 2008;184:1–7.PubMedCrossRef
178.
Debus J, Drings P, Baurecht W, Angermund R. Prospective, randomized, controlled, and open study in primarily inoperable, stage III non-small cell lung cancer (NSCLC) patients given sequential radiochemotherapy with or without epoetin alfa. Radiother Oncol. 2014;112:23–9.PubMedCrossRef
179.
Blohmer JU, Paepke S, Sehouli J, Boehmer D, Kolben M, Wurschmidt F, et al. Randomized phase III trial of sequential adjuvant chemoradiotherapy with or without erythropoietin Alfa in patients with high-risk cervical cancer: results of the NOGGO-AGO intergroup study. J Clin Oncol. 2011;29:3791–7.PubMedCrossRef
180.
Doleschel D, Rix A, Arns S, Palmowski K, Gremse F, Merkle R, et al. Erythropoietin improves the accumulation and therapeutic effects of carboplatin by enhancing tumor vascularization and perfusion. Theranostics. 2015;5:905–18.PubMedPubMedCentralCrossRef
181.
Angiolillo AL, Davenport V, Bonilla MA, van de Ven C, Ayello J, Militano O, et al. A phase I clinical, pharmacologic, and biologic study of thrombopoietin and granulocyte colony-stimulating factor in children receiving ifosfamide, carboplatin, and etoposide chemotherapy for recurrent or refractory solid tumors: a children’s oncology group experience. Clin Cancer Res. 2005;11:2644–50.PubMedCrossRef
182.
Wang C, Zhang B, Wang S, Zhang J, Liu Y, Wang J, et al. Recombinant human thrombopoietin promotes hematopoietic reconstruction after severe whole body irradiation. Sci Rep. 2015;5:1–12.
183.
Ara G, Watkins BA, Zhong H, Hawthorne TR, Karkaria CE, Sonis ST, et al. Velafermin (rhFGF-20) reduces the severity and duration of hamster cheek pouch mucositis induced by fractionated radiation. Int J Radiat Biol. 2008;84:401–12.PubMedCrossRef
184.
Kim MR, Lee J, An YS, Jin YB, Park IC, Chung E, et al. TGFβ1 protects cells from gamma-IR by enhancing the activity of the NHEJ repair pathway. Mol Cancer Res. 2015;13:319–329.
185.
Russell JS, Brown JM. The irradiated tumor microenvironment: role of tumor-associated macrophages in vascular recovery. Front Physiol. 2013;4:157.PubMedPubMedCentralCrossRef
186.
Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest. 2010;120:694–705.PubMedPubMedCentralCrossRef
187.
Ahn GO, Brown JM. Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells. Cancer Cell. 2008;13:193–205.PubMedPubMedCentralCrossRef
188.
Ahn GO, Tseng D, Liao CH, Dorie MJ, Czechowicz A, Brown JM. Inhibition of Mac-1 (CD11b/CD18) enhances tumor response to radiation by reducing myeloid cell recruitment. Proc Natl Acad Sci U S A. 2010;107:8363–8.PubMedPubMedCentralCrossRef
189.
Shiao SL, Ruffell B, DeNardo DG, Faddegon BA, Park CC, Coussens LM. TH2-polarized CD4(+) T cells and macrophages limit efficacy of radiotherapy. Cancer Immunol Res. 2015;3:518–25.PubMedPubMedCentralCrossRef
190.
Arany PR, Flanders KC, DeGraff W, Cook J, Mitchell JB, Roberts AB. Absence of Smad3 confers radioprotection through modulation of ERK-MAPK in primary dermal fibroblasts. J Dermatol Sci. 2007;48:35–42.PubMedPubMedCentralCrossRef
191.
Vanpouille-Box C, Diamond JM, Pilones KA, Zavadil J, Babb JS, Formenti SC, et al. TGFbeta is a master regulator of radiation therapy-induced antitumor immunity. Cancer Res. 2015;75:2232–42.PubMedPubMedCentralCrossRef
192.
Pietraszkiewicz H, Shaw J. UTL-5g lowers levels of TGF-β and TNF-α elevated by lung irradiation and does not affect tumor-response to irradiation. Am J Biomed Sci. 2014;6:157–65.
193.
Park JH, Ryu SH, Choi EK, Ahn SD, Park E, Choi KC, et al. SKI2162, an inhibitor of the TGF-beta type I receptor (ALK5), inhibits radiation-induced fibrosis in mice. Oncotarget. 2015;6:4171–9.PubMedPubMedCentralCrossRef
194.
Koshy M, Rich SE, Mahmood U, Kwok Y. Declining use of radiotherapy in stage I and II Hodgkin’s disease and its effect on survival and secondary malignancies. Int J Radiat Oncol Biol Phys. 2012;82:619–25.PubMedCrossRef
195.
Scott BR, Walker DM, Tesfaigzi Y, Schollnberger H, Walker V. Mechanistic basis for nonlinear dose-response relationships for low-dose radiation-induced stochastic effects. Nonlinearity Biol Toxicol Med. 2003;1:93–122.PubMedPubMedCentralCrossRef
196.
Grantzau T, Overgaard J. Risk of second non-breast cancer after radiotherapy for breast cancer: a systematic review and meta-analysis of 762,468 patients. Radiother Oncol. 2015;114:56–65.PubMedCrossRef
197.
Zelefsky MJ, Pei X, Teslova T, Kuk D, Magsanoc JM, Kollmeier M, et al. Secondary cancers after intensity modulated radiotherapy, brachytherapy and radical prostatectomy for the treatment of prostate cancer: incidence and cause-specific survival outcomes according to the initial treatment intervention. BJU Int. 2012;110:1696–701.PubMedCrossRef
198.
Doi K, Mieno MN, Shimada Y, Yonehara H, Yoshinaga S. Meta-analysis of second cancer risk after radiotherapy among childhood cancer survivors. Radiat Prot Dosim. 2011;146:263–7.CrossRef
199.
Wiltink LM, Nout RA, Fiocco M, et al. No increased risk of second cancer after radiotherapy in patients treated for rectal or endometrial cancer in the randomized TME, PORTEC-1, and PORTEC-2 trials. J Clin Oncol. 2014;58:6693.
200.
Ozsahin M, Crompton NE, Gourgou S, Kramar A, Li L, Shi Y, et al. CD4 and CD8 T-lymphocyte apoptosis can predict radiation-induced late toxicity: a prospective study in 399 patients. Clin Cancer Res. 2005;11:7426–33.PubMedCrossRef
201.
Shim G, Ricoul M, Hempel WM, Azzam EI, Sabatier L. Crosstalk between telomere maintenance and radiation effects: a key player in the process of radiation-induced carcinogenesis. Mutat Res, Rev Mutat Res. 2014;760:1–17.CrossRef
202.
Gramatges MM, Liu Q, Yasui Y, Okcu MF, Neglia JP, Strong LC, et al. Telomere content and risk of second malignant neoplasm in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Clin Cancer Res. 2014;20:904–11.PubMedCrossRef
203.
M’Kacher R, Girinsky T, Colicchio B, Ricoul M, Dieterlen A, Jeandidier E, et al. Telomere shortening: a new prognostic factor for cardiovascular disease post-radiation exposure. Radiat Prot Dosim. 2015;164:134–7.CrossRef
204.
Mirjolet C, Boidot R, Saliques S, Ghiringhelli F, Maingon P, Crehange G. The role of telomeres in predicting individual radiosensitivity of patients with cancer in the era of personalized radiotherapy. Cancer Treat Rev. 2015;41:354–60.PubMedCrossRef
205.
Bystrom LM, Guzman ML, Rivella S. Iron and reactive oxygen species: friends or foes of cancer cells? Antioxid Redox Signaling. 2014;20:1917–24.CrossRef
206.
Zhang C, Liu G, Huang M. Ribonucleotide reductase metallocofactor: assembly, maintenance and inhibition. Front Biol (Beijing, China). 2014;9:104–13.
207.
Yao K, Patel R, Ferris G, Oleinick NL. Triapine enhances radiosensitivity of HPV negative head and neck squamous cell carcinoma cells. Int J Radiat Oncol Biol Phys. 2015;93:E513–4.CrossRef
208.
Kumar IP, Goel HC. Iron chelation and related properties of Podophyllum hexandrum, a possible role in radioprotection. Indian J Exp Biol. 2000;38:1003–6.PubMed
209.
Persson HL. Radiation-induced lysosomal iron reactivity: implications for radioprotective therapy. IUBMB Life. 2006;58:395–401.PubMedCrossRef
210.
Egan LJ, Eckmann L, Greten FR, Chae S, Li ZW, Myhre GM, et al. IkappaB-kinasebeta-dependent NF-kappaB activation provides radioprotection to the intestinal epithelium. Proc Natl Acad Sci U S A. 2004;101:2452–7.PubMedPubMedCentralCrossRef
211.
Riehl TE, Newberry RD, Lorenz RG, Stenson WF. TNFR1 mediates the radioprotective effects of lipopolysaccharide in the mouse intestine. Am J Physiol Gastrointest Liver Physiol. 2004;286:G166–73.PubMedCrossRef
212.
Burdelya LG, Krivokrysenko VI, Tallant TC, Strom E, Gleiberman AS, Gupta D, et al. An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models. Science. 2008;320:226–30.PubMedPubMedCentralCrossRef
213.
Daroczi B, Kari G, Ren Q, Dicker AP, Rodeck U. Nuclear factor kappaB inhibitors alleviate and the proteasome inhibitor PS-341 exacerbates radiation toxicity in zebrafish embryos. Mol Cancer Ther. 2009;8:2625–34.PubMedPubMedCentralCrossRef
214.
Alexeev V, Lash E, Aguillard A, Corsini L, Bitterman A, Ward K, et al. Radiation protection of the gastrointestinal tract and growth inhibition of prostate cancer xenografts by a single compound. Mol Cancer Ther. 2014;13:2968–77.PubMedPubMedCentralCrossRef
215.
Beg AA, Baltimore D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science. 1996;274:782–4.PubMedCrossRef
216.
Izzo JG, Malhotra U, Wu TT, Ensor J, Luthra R, Lee JH, et al. Association of activated transcription factor nuclear factor kappab with chemoradiation resistance and poor outcome in esophageal carcinoma. J Clin Oncol. 2006;24:748–54.PubMedCrossRef
217.
Zhang Y, Wei Y, Zhu Z, Gong W, Liu X, Hou Q, et al. Icariin enhances radiosensitivity of colorectal cancer cells by suppressing NF-kB activity. Cell Biochem Biophys. 2014;69:303–10.PubMedCrossRef
218.
Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, et al. Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 2006;354:567–78.PubMedCrossRef
219.
Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK, et al. Radiotherapy plus cetuximab for ocoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol. 2010;11:21–8.PubMedCrossRef
220.
Fan Z, Baselga J, Masui H, Mendelsohn J. Antitumor effect of anti-epidermal growth factor receptor monoclonal antibodies plus cis-diamminedichloroplatinum on well established A431 cell xenografts. Cancer Res. 1993;53:4637–42.PubMed
221.
Huang SM, Bock JM, Harari PM. Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. Cancer Res. 1999;59:1935–40.PubMed
222.
Debucquoy A, Machiels JP, McBride WH, Haustermans K. Integration of epidermal growth factor receptor inhibitors with preoperative chemoradiation. Clin Cancer Res. 2010;16:2709–14.PubMedCrossRef
223.
Ang KK, Zhang Q, Rosenthal DI, Nguyen-Tan PF, Sherman EJ, Weber RS, et al. Randomized phase III trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for stage III to IV head and neck carcinoma: RTOG 0522. J Clin Oncol. 2014;32:2940–50.PubMedPubMedCentralCrossRef
224.
225.
Zhang LJ, Yan YJ, Liao PY, Margetic D, Wang L, Chen ZL. Synthesis and antitumor activity evaluation of a novel porphyrin derivative for photodynamic therapy in vitro and in vivo. Tumor Biol. 2015;37:1–11.
226.
Nyst HJ, Wildeman MA, Indrasari SR, Karakullukcu B, van Veen RLP, Adham M, et al. Temoporfin mediated photodynamic therapy in patients with local persistent and recurrent nasopharyngeal carcinoma after curative radiotherapy: a feasibility study. Photodiagn Photodyn Ther. 2012;9:274–81.CrossRef
227.
Moulder JE, Fish BL. Angiotensin converting enzyme inhibitor captopril does not prevent acute gastrointestinal radiation damage in the rat. Radiat Oncol Invest. 1997;5:50–3.CrossRef
228.
Bracci S, Valeriani M, Agolli L, De Sanctis V, Maurizi Enrici R, Osti MF. Renin-angiotensin system inhibitors might help to reduce the development of symptomatic radiation pneumonitis after stereotactic body radiotherapy for lung cancer. Clin Lung Cancer. 2015;17:189–197.
229.
Zhao DY, Jacobs KM, Hallahan DE, Thotala D. Silencing Egr1 attenuates radiation-induced apoptosis in normal tissues while killing cancer cells and delaying tumor growth. Mol Cancer Ther. 2015;14:2343–52.PubMedPubMedCentralCrossRef
230.
Allen B, Marcu L, & Bezak E. Biomedical physics in radiotherapy for cancer. Clayton: CSIRO PUBLISHING; 2012.
231.
Prasad KN. Radiation injury prevention and mitigation in humans. Abingdon: Taylor & Francis; 2012.
232.
Moding EJ, Kastan MB, Kirsch DG. Strategies for optimizing the response of cancer and normal tissues to radiation. Nat Rev Drug Discovery. 2013;12:526–42.PubMedCrossRef
233.
Geiger H, Pawar SA, Kerschen EJ, Nattamai KJ, Hernandez I, Liang HP, et al. Pharmacological targeting of the thrombomodulin-activated protein C pathway mitigates radiation toxicity. Nat Med. 2012;18:1123–9.PubMedPubMedCentralCrossRef
234.
Singh VK, Wise SY, Fatanmi OO, Beattie LA, Ducey EJ, Seed TM. Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice. J Radiat Res. 2014;55:41–53.PubMedCrossRef
235.
Christensen R, Alsner J, Brandt Sorensen F, Dagnaes-Hansen F, Kolvraa S, Serakinci N. Transformation of human mesenchymal stem cells in radiation carcinogenesis: long-term effect of ionizing radiation. Regener Med. 2008;3:849–61.CrossRef
236.
Cruet-Hennequart S, Drougard C, Shaw G, Legendre F, Demoor M, Barry F, et al. Radiation-induced alterations of osteogenic and chondrogenic differentiation of human mesenchymal stem cells. PLoS One. 2015;10:e0119334.PubMedPubMedCentralCrossRef
237.
Lenarczyk M, Su J, Haworth ST, Komorowski R, Fish BL, Migrino RQ, et al. Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation. Pharmacol Res Perspect. 2015;3:e00145.PubMedPubMedCentralCrossRef
238.
O’Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, et al. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple negative breast cancer. J Clin Oncol. 2014;34:3840–3847.
239.
Patel AG, De Lorenzo SB, Flatten KS, Poirier GG, Kaufmann SH. Failure of iniparib to inhibit poly(ADP- Ribose) polymerase in vitro. Clin Cancer Res. 2012;18:1655–62.PubMedPubMedCentralCrossRef
240.
Barber LJ, Davies MN, Gerlinger M. Dissecting cancer evolution at the macro-heterogeneity and micro heterogeneity scale. Curr Opin Genet Dev. 2015;30:1–6.PubMedPubMedCentralCrossRef
Metadaten
Titel
Emerging targets for radioprotection and radiosensitization in radiotherapy
verfasst von
Sumit Kumar
Rajnish Kumar Singh
Ramovatar Meena
Publikationsdatum
19.06.2016
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 9/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5117-8

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