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A review of radiation genomics: integrating patient radiation response with genomics for personalised and targeted radiation therapy

  • Lu Xu (a1) (a2), Beverley Osei (a3) (a2) and Ernest Osei (a2) (a4) (a5) (a6)



The success of radiation therapy for cancer patients is dependent on the ability to deliver a total tumouricidal radiation dose capable of eradicating all cancer cells within the clinical target volume, however, the radiation dose tolerance of the surrounding healthy tissues becomes the main dose-limiting factor. The normal tissue adverse effects following radiotherapy are common and significantly impact the quality of life of patients. The likelihood of developing these adverse effects following radiotherapy cannot be predicted based only on the radiation treatment parameters. However, there is evidence to suggest that some common genetic variants are associated with radiotherapy response and the risk of developing adverse effects. Radiation genomics is a field that has evolved in recent years investigating the association between patient genomic data and the response to radiation therapy. This field aims to identify genetic markers that are linked to individual radiosensitivity with the potential to predict the risk of developing adverse effects due to radiotherapy using patient genomic information. It also aims to determine the relative radioresponse of patients using their genetic information for the potential prediction of patient radiation treatment response.

Methods and materials

This paper reports on a review of recent studies in the field of radiation genomics investigating the association between genomic data and patients response to radiation therapy, including the investigation of the role of genetic variants on an individual’s predisposition to enhanced radiotherapy radiosensitivity or radioresponse.


The potential for early prediction of treatment response and patient outcome is critical in cancer patients to make decisions regarding continuation, escalation, discontinuation, and/or change in treatment options to maximise patient survival while minimising adverse effects and maintaining patients’ quality of life.


Corresponding author

Author for correspondence: Ernest Osei, Grand River Regional Cancer Centre, 835 King Street West, Kitchener, Ontario N2G1G3, Canada. Tel: 519 749 4300. E-mail:


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Cite this article: Xu L, Osei B, Osei E. (2019) A review of radiation genomics: integrating patient radiation response with genomics for personalised and targeted radiation therapy. Journal of Radiotherapy in Practice18: 198–209. doi: 10.1017/S1460396918000547



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1. Guo, Z, Shu, Y, Zhou, H, Zhang, W, Wang, H. Radiogenomics helps to achieve personalized therapy by evaluating patient responses to radiation treatment. Carcinogenesis 2015; 36 (3): 307317.
2. Kerns, S L, West, C M, Andreassen, C N et al. Radiogenomics: the search for genetic predictors of radiotherapy response. Future Oncol 2014; 10 (15): 23912406.
3. Naqa, I E, Kerns, S L, Coates, J et al. Radiogenomics and radiotherapy response modeling. Phys Med Biol 2017; 62: R179R206.
4. West, C M, Barnett, G C. Genetics and genomics of radiotherapy toxicity: towards prediction. Genome Med 2001; 3 (8): 5267.
5. Kerns, S L, Ruysscher, D, Andreassen, C N et al. STROGAR – strengthening the reporting of genetic association studies in radiogenomics. Radiother Oncol 2014; 110 (1): 182188.
6. Fan, C, Tang, Y, Wang, J et al. Role of long noncoding RNAs in glucose metabolism in cancer. Mol Cancer 2017; 16: 130141.
7. Rattay, T, Talbot, C J. Finding the genetic determinants of adverse reactions to radiotherapy. Clin Oncol 2014; 26: 301308.
8. Kerns, S L, Kundu, S, Oh, J H et al. The prediction of radiotherapy toxicity using single nucleotide polymorphism (SNP)-based models: a step towards prevention. Semin Radiat Oncol 2015; 25 (4): 281291.
9. Bai, H X, Lee, A M, Yang, L et al. Imaging genomics in cancer research: limitations and promises. Br J Radiol 2016; 89 (1061): 20151030.
10. Wu, J, Tha, K K, Xing, L, Li, R. Radiomics and radiogenomics for precision radiotherapy. J Radiat Res 2018; 59 (suppl_1): i2531.
11. Incoronato, M, Aiello, M, Infante, T et al. Radiogenomic analysis of oncological data: a technical survey. Int J Mol Sci 2017; 18 (4): 805833.
12. Zinn, P O, Mahmood, Z, Elbanan, M G, Colen, R R. Imaging genomics in gliomas. Canc J 2015; 21 (3): 225234.
13. ElBanan, M G, Amer, A M, Zinn, P O, Colen, R R. Imaging genomics of Glioblastoma: state of the art bridge between genomics and neuroradiology. Neuroimag Clin 2015; 25 (1): 141153.
14. Mazurowski, M A. Radiogenomics: what it is and why it is important. J Am Coll Radiol 2015; 12 (8): 862866.10.1016/j.jacr.2015.04.019
15. Barnett, G C, Coles, C E, Elliot, R M et al. Independent validation of genes and polymorphisms reported to be associated with radiation toxicity: a prospective analysis study. Lancet Oncol 2012; 13 (1): 6577.
16. Rosenstein, B S, West, C M, Bentzen, S M, Alsner, J, Andreassen, C N, Azria, D. Radiogenomics: radiobiology enters the era of big data and team science. Int J Radiat Oncol Biol Phys 2014; 89 (4): 709713.
17. Lambin, P, Leikennaar, R T H, Deist, T M, Peerlings, J, de Jong, E E C, van Timmeren, J. Radiomics: the bridge between medical imaging and personalized medicine. Nat Rev Clin Oncol 2017; 14 (12): 749762.
18. Pawlik, T M, Keyomarsi, K. Role of cell cycle in mediating sensitivity to radiotherapy. Int J Radiat Oncol Biol Phys 2004; 59 (4): 928942.
19. Suit, H. The gray lecture 2001: coming technical advances in radiation oncology. Int J Radiat Oncol Biol Phys 2002; 15 (4): 798809.
20. Rosenstein, B S. Radiogenomics: identification of genomic predictors for radiation toxicity. Sem Radiat Oncol 2017; 27 (4): 300309.
21. Brenner, H. Long-term survival rates of cancer patients achieved by the end of the 20th century: a period analysis. Lancet 2002; 360 (9340): 11311135.
22. Emami, B, Lyman, J, Brown, A et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991; 21: 109122.
23. Azria, D, Lapierre, A, Gourgou, S et al. Data-based radiation oncology: design of clinical trials in the toxicity biomarkers era. Front Oncol 2017; 7: 8394.
24. Group, B D W. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 2001; 69 (3): 8995.
25. Andreassen, C N, Alsner, J, Overgaard, J. Does variability in normal tissue reactions after radiotherapy have a genetic basis – where and how to look for it? Radiother Oncol 2002; 64 (2): 131140.
26. Andreassen, C N, Schack, L M, Laursen, L V, Alsner, J. Radiogenomics–current status, challenges and future directions. Canc Lett 2016; 382 (1): 127136.
27. Vaisnav, M, Xing, C, Ku, H C et al. Genome-wide association analysis of radiation resistance in Drosophila melanogaster . PLoS ONE 2014; 9 (8): e104858.
28. Barnett, G C, Thompson, D, Fachal, L et al. A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity. Radiother Oncol 2014; 111: 178185.
29. Scott, D. Chromosomal radiosensitivity and low penetrance predisposition to cancer. Cytogenet Genome Res 2004; 104: 365370.
30. Barnett, G C, Kerns, S L, Noble, D J, Dunning, A M, West, C M, Brunet, N G. Incorporating genetic biomarkers into predictive models of normal tissue toxicity. Clin Oncol 2015; 27 (10): 579587.
31. Kelsey, C R, Jackson, I L, Langdon, S et al. Analysis of single nucleotide polymorphisms and radiation sensitivity of the lung assessed with an objective radiologic endpoint. Clin Lung Cancer 2013; 14 (3): 267274.
32. Kerns, S L, Ostrer, H, Rosenstein, B S. Radiogenomics: using genetics to identify cancer patients at risk for development of adverse effects following radiotherapy. Cancer Discov 2014; 4 (2): 155165.
33. Andreassen, C N. The future has begun in radiogenomics!. Radiother Oncol 2014; 111 (2): 165167.
34. Talbot, C J, Tanteles, G A, Barnett, G C et al. A replicated association between polymorphisms near TNFalpha and risk for adverse reactions to radiotherapy. Br J Canc 2012; 107 (4): 748753.
35. Seibold, P, Behrens, S, Schmezer, P et al. XRCC1 polymorphism associated with late toxicity after radiation therapy in breast cancer patients. Int J Radiat Oncol Biol Phys 2015; 92 (5): 10841092.
36. Pratesi, N, Mangoni, M, Mancini, I et al. Association between single nucleotide polymorphisms in XRCC1 and RAD51 genes and clinical radiosensitivity in head and neck cancer. Radiother Oncol 2011; 99: 356361.
37. Nogueira, A, Catarino, R, Faustino, I et al. Role of RAD51 G172T polymorphism in the clinical outcome of cervical cancer patients under concomitant chemoradiotherapy. Gene 2012; 504: 279283.
38. Venkatesh, G H, Manjunath, V B, Mumbrekar, K D et al. Polymorphisms in radio-responsive genes and its association with acute toxicity among head and neck cancer patients. PLoS One 2014; 9 (3): e89079.
39. Yin, M, Liao, Z X, Huang, Y J et al. Polymorphisms of homologous recombination genes and clinical outcomes of non-small lung cancer patients treated with definitive radiotherapy. PLoS One 2011; 6: e20055.
40. Yang, M, Zhang, L, Bi, N et al. Association of P53 and ATM polymorphisms with risk of radiation-induced pneumonitis in lung cancer patients treated with radiotherapy. Int J Radiat Oncol Biol Phys 2011; 79 (5): 14021407.
41. Chang-Claude, J, Ambrosone, C B, Lilla, C et al. Genetic polymorphisms in DNA repair and damage response genes and late normal tissue complications of radiotherapy for breast cancer. Br J Canc 2009; 100: 16801686.
42. Xie, X, Wang, H, Jin, H et al. Expression of pAkt affects p53 codon 72 polymorphism-based prediction of response to radiotherapy in nasopharyngeal carcinoma. Radiat Oncol 2013; 8: 117127.
43. Cintra, H S, Pinezi, J C D, Machado, G D P et al. Investigation of genetic polymorphisms related to outcome of radiotherapy for prostate cancer patients. Dis Markers 2013; 35 (6): 701710.
44. Mangoni, M, Bisanzi, S, Carozzi, F et al. Association between genetic polymorphisms in the XRCC1, XRCC3, XPD, GSTM1, GSTT1, MSH2, MLH1, MSH3, and MGMT genes and radiosensitivity in breast cancer patients. Int J Radiat Oncol Biol Phys 2011; 81 (1): 5258.
45. Zyla, J, Finnon, P, Bulman, R, Bouffler, S, Badie, C, Polanska, J. Seeking genetic signature of radiosensitivity – a novel method for data analysis in case of small sample sizes. Theoret Biol Med Model 2014; 11 (Suppl 1): S2S18.
46. Martin, L M, Marples, B, Davies, A M et al. DNA mismatch repair protein MSH2 dictates cellular survival in response to low dose radiation in endometrial carcinoma cells. Canc Lett 2013; 335: 1925.
47. Bernier, J, Poortmans, P. Clinical relevance of normal and tumour cell radiosensitivity in BRCA1/BRCA2 mutation carriers: a review. Breast 2015; 24 (2): 100106.
48. Park, H, Choi, D H, Noh, J M et al. Acute skin toxicity in Korean breast cancer patients carrying BRCA mutations. Int J Radiat Biol 2014; 90 (1): 9094.
49. Baert, A, Depuydt, J, Van Maerken, T et al. Analysis of chromosomal radiosensitivity of healthy BRCA2 mutation carriers and non-carriers in BRCA families with the G2 micronucleus assay. Oncol Rep 2017; 37 (3): 13791386.
50. Ernestos, B, Nikolaos, P, Koulis, G et al. Increased chromosomal radiosensitivity in women carrying BRCA1/BRCA2 mutations assessed with the G2 assay. Int J Radiat Oncol Biol Phys 2010; 76 (4): 11991205.
51. Pierce, L J, Strawderman, M, Narod, S A et al. Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations. J Clin Oncol 2000; 18 (19): 33603369.
52. Moding, E J, Lee, C L, Castle, K D et al. Atm deletion with dual recombinase technology preferentially radiosensitizes tumor endothelium. J Clin Investig 2014; 124 (8): 33253338.
53. Zhang, L, Yang, M, Bi, N et al. ATM polymorphisms are associated with risk of radiation-induced pneumonitis. Int J Radiat Oncol Biol Phys 2010; 77 (5): 13601368.
54. Raabe, A, Derda, K, Reuther, S et al. Association of single nucleotide polymorphisms in the genes ATM, GSTP1, SOD2, TGFB1, XPD and XRCC1 with risk of severe erythema after breast conserving radiotherapy. Radiat Oncol 2012; 7 (1): 65–54.
55. Cintra, H S, Pinezi, J C, Machado, G D et al. Investigation of genetic polymorphisms related to the outcome of radiotherapy for prostate cancer patients. Dis Markers 2013; 35 (6): 701710.
56. Thacker, J, Zdzienicka, M Z. The mammalian XRCC genes: their roles in DNA repair and genetic stability. DNA Rep 2003; 2 (6): 655672.
57. Yin, M, Liao, Z, Liu, Z et al. Functional polymorphisms of base excision repair genes XRCC1 and APEX1 predict risk of radiation pneumonitis in patients with non–small cell lung cancer treated with definitive radiation therapy. Int J Radiat Oncol Biol Phys 2011; 81 (3): e67e73.
58. Burri, R J, Stock, R G, Cesaretti, J A et al. Association of single nucleotide polymorphisms in SOD2, XRCC1 and XRCC3 with susceptibility for the development of adverse effects resulting from radiotherapy for prostate cancer. Radiat Res 2008; 170 (1): 4959.
59. Cheuk, I W, Yip, S P, Kwong, D L, Wu, V W. Association of XRCC1 and XRCC3 gene haplotypes with the development of radiation‑induced fibrosis in patients with nasopharyngeal carcinoma. Mol Clin Oncol 2014; 2 (4): 553558.
60. Andreassen, C N, Alsner, J. Genetic variants and normal tissue toxicity after radiotherapy: a systematic review. Radiother Oncol 2009; 92: 299309.
61. Andreassen, C N. Searching for genetic determinants of normal tissue radiosensitivity – are we on the right track? Radiother Oncol 2010; 97 (1): 18.
62. Andreassen, C N, Schack, L M, Laursen, L V, Alsner, J. Radiogenomics-current status, challenges, and future directions. Canc Lett 2016; 382 (1): 127136.
63. Sachidanandam, R, Weissman, D, Schmidt, S C et al. A map of human genome sequence variation containing 1·42 million single nucleotide polymorphisms. Nature 2001; 409 (6822): 928933.
64. Kerns, S L, Kundu, S, Oh, J H et al. The prediction of radiotherapy toxicity using single nucleotide polymorphism-based models: a step toward prevention. Semin Radiat Oncol 2015; 25: 281291.
65. Herskind, C, Talbot, C J, Kerns, S L, Veldwijk, M R, Rosenstein, B S, West, C M. Radiogenomics: a systems biology approach to understanding genetic risk factors for radiotherapy toxicity? Canc Lett 2016; 382 (1): 95109.
66. West, C, Rosenstein, B S. Establishment of a radiogenomics consortium. Radiother Oncol 2010; 94: 117124.
67. Barnett, G C, West, C M, Dunning, A M et al. Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nat Rev Canc 2009; 9: 134142.
68. Edwards, S L, Beesley, J, French, J D, Dunning, A M. Beyond GWASs: illuminating the dark road from association to function. Am J Hum Genet 2013; 93: 779797.
69. Zhang, F, Gu, W, Hurles, M E, Lupski, J R. Copy number variation in human health, disease, and evolution. Ann Rev Genom Human Genet 2009; 10: 451481.
70. Stranger, B E, Forrest, M S, Dunning, M et al. Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 2007; 315: 848853.
71. Eustace, A, Mani, N, Span, P N et al. A 26-gene hypoxia signature predicts benefit from hypoxia-modifying therapy in laryngeal cancer but not bladder cancer. Clin . Canc Res 2013; 19: 48794888.
72. Yang, L, Taylor, J, Eustace, A et al. A Gene signature for selecting benefit from hypoxia modification of radiotherapy for high risk bladder cancer patients. Clin Canc Res 2017; 23 (16): 47614768.
73. Yard, B D, Adams, D J, Chie, E K et al. A genetic basis for the variation in the vulnerability of cancer to DNA damage. Nat Commun 2016; 7: 11428.
74. Dickey, J S, Zemp, F J, Martin, O A, Kovalchuk, O. The role of miRNA in the direct and indirect effects of ionizing radiation. Radiat Environ Biophys 2011; 50: 491499.
75. Kovalchuk, O, Zemp, F J, Filkowski, J N et al. microRNAome changes in bystander three-dimensional human tissue models suggest priming of apoptotic pathways. Carcinogenesis 2010; 31: 18821888.
76. Dickey, J S, Zemp, F J, Altamirano, A, Sedelnikova, O A, Bonner, W M, Kovalchuk, O. H2AX phosphorylation in response to DNA double-strand break formation during bystander signalling: effect of microRNA knockdown. Radiat Prot Dosimetry 2011; 143: 264269.
77. Wang, W, Luo, Y-P. MicroRNAs in breast cancer: oncogene and tumor suppressors with clinical potential. J Zhejiang Univ 2015; 16: 1831.
78. O’Leary, V B, Ovsepian, S V, Carrascosa, L G et al. PARTICLE, a triplex-forming long ncRNA, regulates locus-specific methylation in response to low-dose irradiation. Cell Rep 2015; 11: 474485.
79. Zhang, Y, He, Q, Hu, Z et al. Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer. Nat Struct Mol Biol 2016; 23: 522530.
80. Wang, J, Xu, J, Fu, J et al. MiR-29a regulates radiosensitivity in human intestinal cells by targeting PTEN gene. Radiat Res 2016; 186 (3): 292301.
81. Weigel, C, Veldwijk, M R, Oakes, C C et al. Epigenetic regulation of diacylglycerol kinase alpha promotes radiation-induced fibrosis. Nat Commun 2016; 7: 10893.
82. Weigel, C, Schmezer, P, Plass, C, Popanda, O. Epigenetics in radiation-induced fibrosis. Oncogene 2015; 34: 21452155.
83. Merrifield, M, Kovalchuk, O. Epigenetics in radiation biology: a new research frontier. Front Genet 2013; 4: 4056.
84. Ilnytskyy, Y, Kovalchuk, O. Non-targeted radiation effects-an epigenetic connection. Mutat Res 2011; 714: 113125.
85. Ilnytskyy, Y, Koturbash, I, Kovalchuk, O. Radiation-induced bystander effects in vivo are epigenetically regulated in a tissue-specific manner. Environ Mol Mutagen 2009; 50: 105113.
86. Imadome, K, Iwakawa, M, Nakawatari, M et al. Subtypes of cervical adenosquamous carcinomas classified by EpCAM expression related to radiosensitivity. Canc Biol Ther 2010; 10: 10191026.
87. Tang, L, Wei, F, Wu, Y et al. Role of metabolism in cancer cell radioresistance and radiosensitization methods. J Exp Clin Canc Res 2018; 37: 87102.
88. Tang, Y, Wang, J, Lian, Y et al. Linking long noncoding RNAs and SWI/SNF complexes to chromatin remodeling in cancer. Mol Canc 2017; 16: 42.
89. Hanahan, D, Weinberg, R A. Hallmarks of cancer: the next generation. Cell 2011; 144: 646674.
90. Yoshida, G J. Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res 2015; 34: 111121.
91. Fang, J, Zhou, S H, Fan, J, Yan, S X. Roles of glucose transporter-1 and the phosphatidylinositol 3kinase/protein kinase B pathway in cancer radioresistance (review). Mol Med Rep 2015; 11: 15731581.
92. Kunkel, M, Moergel, M, Stockinger, M et al. Overexpression of GLUT-1 is associated with resistance to radiotherapy and adverse prognosis in squamous cell carcinoma of the oral cavity. Oral Oncol 2007; 43: 796803.
93. De Schutter, H, Landuyt, W, Verbeken, E, Goethals, L, Hermans, R, Nuyts, S. The prognostic value of the hypoxia markers CA IX and GLUT 1 and the cytokines VEGF and IL 6 in head and neck squamous cell carcinoma treated by radiotherapy +/− chemotherapy. BMC Canc 2005; 5: 4253.
94. Vander Heiden, M G, Cantley, L C, Thompson, C B. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009; 324: 10291033.
95. Li, Z, Zhang, H. Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression. Cell Mol Life Sci 2016; 73: 377392.
96. Li, L, Li, W. Epithelial-mesenchymal transition in human cancer: comprehensive reprogramming of metabolism, epigenetics, and differentiation. Pharmacol Ther 2015; 150: 3346.
97. Bhatt, A N, Chauhan, A, Khanna, S et al. Transient elevation of glycolysis confers radio-resistance by facilitating DNA repair in cells. BMC Canc 2015; 15: 335347.
98. Shimura, T, Noma, N, Sano, Y et al. AKT-mediated enhanced aerobic glycolysis causes acquired radioresistance by human tumor cells. Radiother Oncol 2014; 112: 302307.
99. Fischer, K, Hoffmann, P, Voelkl, S et al. Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood 2007; 109: 38123819.
100. Feng, J, Yang, H, Zhang, Y et al. Tumor cell-derived lactate induces TAZ-dependent upregulation of PD-L1 through GPR81 in human lung cancer cells. Oncogene 2017; 36 (42): 58295839.
101. Hirschhaeuser, F, Sattler, U G, Mueller-Klieser, W. Lactate: a metabolic key player in cancer. Canc Res 2011; 71: 69216925.
102. Halestrap, A P. The monocarboxylate transporter family–structure and functional characterization. IUBMB Life 2012; 64: 19.
103. Fujiwara, S, Wada, N, Kawano, Y et al. Lactate, a putative survival factor for myeloma cells, is incorporated by myeloma cells through monocarboxylate transporters 1. Exp Hematol Oncol 2015; 4: 1220.
104. Bala, M, Goel, H C. Modification of low dose radiation induced radioresistance by 2-deoxy-D-glucose in Saccharomyces cerevisiae: mechanistic aspects. J Radiat Res 2007; 48: 335346.
105. Dwarkanath, B S, Zolzer, F, Chandana, S et al. Heterogeneity in 2-deoxy-D-glucose-induced modifications in energetics and radiation responses of human tumor cell lines. Int J Radiat Oncol Biol Phys 2001; 50: 10511061.
106. Toulany, M, Schickfluss, T A, Eicheler, W, Kehlbach, R. Schittek B., Rodemann H. P. Impact of oncogenic K-RAS on YB-1 phosphorylation induced by ionizing radiation. Breast Canc Res 2011; 13: R28.
107. Bur, H, Haapasaari, K M, Turpeenniemi-Hujanen, T et al. Low Rap1-interacting factor 1 and sirtuin 6 expression predict poor outcome in radiotherapy-treated Hodgkin lymphoma patients. Leuk Lymphoma 2018; 59: 679689.
108. Chen, Y, Li, Z, Dong, Z et al. 14-3-3sigma contributes to Radioresistance by regulating DNA repair and cell cycle via PARP1 and CHK2. Mol Cancer Res 2017; 15: 418428.
109. Wei, F, Tang, L, He, Y et al. BPIFB1 (LPLUNC1) inhibits radioresistance in nasopharyngeal carcinoma by inhibiting VTN expression. Cell Death Dis 2018; 9: 432.
110. Wei, F, Wu, Y, Tang, L et al. BPIFB1 (LPLUNC1) inhibits migration and invasion of nasopharyngeal carcinoma by interacting with VTN and VIM. Br J Cancer 2018; 118: 233247.
111. Zhou, R, Wu, Y, Wang, W et al. Circular RNAs (circRNAs) in cancer. Cancer Lett 2018; 425: 134142.
112. Zhang, X, Li, Y, Wang, D, Wei, X. miR-22 suppresses tumorigenesis and improves radiosensitivity of breast cancer cells by targeting Sirt1. Biol Res 2017; 50: 27.
113. Goffart, N, Lombard, A, Lallemand, F et al. CXCL12 mediates glioblastoma resistance to radiotherapy in the subventricular zone. Neuro-Oncology 2017; 19: 6677.
114. Zhang, Y, Xia, M, Jin, K et al. Function of the c-Met receptor tyrosine kinase in carcinogenesis and associated therapeutic opportunities. Mol Cancer 2018; 17: 45.
115. Zhang, H, Luo, H, Jiang, Z et al. Fractionated irradiation-induced EMT-like phenotype conferred radioresistance in esophageal squamous cell carcinoma. J Radiat Res 2016; 57: 370380.
116. Xie, G, Liu, Y, Yao, Q et al. Hypoxia-induced angiotensin II by the lactate-chymase-dependent mechanism mediates radioresistance of hypoxic tumor cells. Sci Rep 2017; 7: 42396.
117. Yang, L, Tang, Y, Xiong, F et al. LncRNAs regulate cancer metastasis via binding to functional proteins. Oncotarget 2017; 9 (1): 14261443.
118. Yoshida, G J, Saya, H. Therapeutic strategies targeting cancer stem cells. Cancer Sci 2016; 107: 511.
119. Osuka, S, Sampetrean, O, Shimizu, T et al. IGF1 receptor signaling regulates adaptive radioprotection in glioma stem cells. Stem cells 2013; 31: 627640.
120. Appukuttan, A, Flacke, J P, Flacke, H, Posadowsky, A, Reusch, H P, Ladilov, Y. Inhibition of soluble adenylyl cyclase increases the radiosensitivity of prostate cancer cells. Biochim Biophys Acta 1842; 2014: 26562663.
121. Hao, J, Graham, P, Chang, L et al. Proteomic identification of the lactate dehydrogenase a in a radioresistant prostate cancer xenograft mouse model for improving radiotherapy. Oncotarget 2016; 7: 7426974285.
122. He, R, Liu, P, Xie, X et al. circGFRA1 and GFRA1 act as ceRNAs in triple negative breast cancer by regulating miR-34a. J Exp Clin Cancer Res 2017; 36: 145157.
123. Li, X, Lu, P, Li, B et al. Sensitization of hepatocellular carcinoma cells to irradiation by miR34a through targeting lactate dehydrogenase A. Mol Med Rep 2016; 13: 36613667.
124. Liu, G, Li, Y I, Gao, X. Overexpression of microRNA-133b sensitizes non-small cell lung cancer cells to irradiation through the inhibition of glycolysis. Oncol Lett 2016; 11: 29032908.
125. Shen, H, Hau, E, Joshi, S, Dilda, P J, McDonald, K L. Sensitization of glioblastoma cells to irradiation by modulating the glucose metabolism. Mol Cancer Ther 2015; 14: 17941804.
126. Lynam-Lennon, N, Maher, S G, Maguire, A et al. Altered mitochondrial function and energy metabolism is associated with a radioresistant phenotype in oesophageal adenocarcinoma. PLoS One 2014; 9: e100738.
127. Fisher, C J, Goswami, P C. Mitochondria-targeted antioxidant enzyme activity regulates radioresistance in human pancreatic cancer cells. Cancer Biol Ther 2008; 7: 12711279.
128. Maus, F, Sakry, D, Biname, F et al. The NG2 proteoglycan protects oligodendrocyte precursor cells against oxidative stress via interaction with OMI/HtrA2. PLoS One 2015; 10: e0137311.
129. Chiou, J-F, Tai, C-J, Wang, Y-H, Liu, T-Z, Jen, Y-M, Shiau, C-Y. Sorafenib induces preferential apoptotic killing of a drug- and radio-resistant help G2 cells through a mitochondria-dependent oxidative stress mechanism. Cancer Biol Ther 2014; 8: 19041913.
130. Alphonse, G, Bionda, C, Aloy, M T, Ardail, D, Rousson, R, Rodriguez-Lafrasse, C. Overcoming resistance to gamma-rays in squamous carcinoma cells by poly-drug elevation of ceramide levels. Oncogene 2004; 23: 27032715.
131. Dong, G, Chen, Q, Jiang, F et al. Diisopropylamine dichloroacetate enhances radiosensitization in esophageal squamous cell carcinoma by increasing mitochondria-derived reactive oxygen species levels. Oncotarget 2016; 7: 6817068178.
132. You, W C, Chiou, S H, Huang, C Y et al. Mitochondrial protein ATPase family, AAA domain containing 3A correlates with radioresistance in glioblastoma. Neuro-Oncology 2013; 15: 13421352.
133. Liu, R, Fan, M, Candas, D et al. CDK1-mediated SIRT3 activation enhances mitochondrial function and tumor radioresistance. Mol Cancer Ther 2015; 14: 20902102.
134. Candas, D, Lu, C L, Fan, M et al. Mitochondrial MKP1 is a target for therapy-resistant HER2-positive breast cancer cells. Cancer Res 2014; 74: 74987509.
135. Li, Y L, Chang, J T, Lee, L Y et al. GDF15 contributes to radioresistance and cancer stemness of head and neck cancer by regulating cellular reactive oxygen species via a SMAD-associated signaling pathway. Oncotarget 2017; 8: 15081528.
136. Shonai, T, Adachi, M, Sakata, K et al. MEK/ERK pathway protects ionizing radiation-induced loss of mitochondrial membrane potential and cell death in lymphocytic leukemia cells. Cell Differ 2002; 9: 963971.
137. Huang, L, Li, B, Tang, S et al. Mitochondrial KATP channels control glioma radioresistance by regulating ROS-induced ERK activation. Mol Neurobiol 2015; 52: 626637.
138. Dong, Q, Sharma, S, Liu, H et al. HDAC inhibitors reverse acquired radio resistance of KYSE-150R esophageal carcinoma cells by modulating Bmi-1 expression. Toxicol Lett 2014; 224: 121129.
139. Kuwahara, Y, Roudkenar, M H, Suzuki, M et al. The involvement of mitochondrial membrane potential in cross-resistance between radiation and docetaxel. Int J Radiat Oncol Biol Phys 2016; 96: 556565.
140. Scaife, J E, Barnett, G C, Noble, D J et al. Exploiting biological and physical determinants of radiotherapy toxicity to individualize treatment. Br J Radiol 2015; 88 (1051): 20150172.
141. Seal, S, Thompson, D, Renwick, A et al. Truncating mutations in the Fanconi anemia J gene VRIP1 are low-penetrance breast cancer susceptibility alleles. Nat Genet 2006; 38 (11): 12391241.
142. Levitus, M, Waisfisz, Q, Godthelp, B C et al. The DNA helicase BRIP1 is defective in Fanconi anemia complementation group. J Nat Genet 2005; 37 (9): 934935.
143. Karppinen, S M, Barkardottir, R B, Backenhorn, K et al. Nordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignancies. J Med Genet 2006; 43: 856862.
144. Rudolf de Beer, H, Llobet, S G, van Vugt, M. Controlling the response to DNA damage by APC/C-Cdh1. Cell Mol Life Sci 2016; 73: 949960.
145. Wang, C, Su, Z, Hou, H et al. Inhibition of anaphase-promoting complex by silence APC/C-Cdh1 to enhance radiosensitivity of nasopharyngeal carcinoma cells. J Cell Biochem 2017; 118: 31503157.
146. Bayens, A, Claes, K, Willems, P, De Ruyck, K, Thierens, H, Vral, A. Chromosomal radiosensitivity of breast cancer with a CHEK2 mutation. Canc Genet Cytogenet 2005; 163: 106112.
147. Zhang, Q, Si, S, Schoen, S, Jin, X B, Chen, J, Wu, G. Folliculin deficient renal cancer cells show higher radiosensitivity through autophagic cell death. J Urol 2014; 191: 18801888.
148. Ni, J, Cozzi, P, Hao, J et al. Epithelial cell adhesion molecule (EpCAM) is associated with prostate cancer metastasis and chemo/radioresistance via the PI3K/Akt/mTOR signalling pathway. Int J Biochem Cell Biol 2013; 45: 27362748.
149. Yan, T, Seo, Y, Kinsella, T J. Differential cellular responses to prolonged LDR-IR in MLH1-proficient and MLH1-deficient colorectal cancer HCT116 cells. Clin Canc Res 2009; 15 (22): 69126920.
150. Wang, Q, Xiao, Z, Lin, Z et al. Autophagy influences the low-dose hyper-radiosensitivity of human lung adenocarcinoma cells by regulating MLH1. Int J Radiation Biol 2017; 93 (6): 600606.
151. Yin, J, Lu, C, Gu, J et al. Common genetic variants in cell cycle pathway are associated with survival in stage III-IV non-small-cell lung cancer. Carcinogenesis 2011; 32 (12): 18671871.
152. Yang, M, Zhang, L, Bi, N et al. Association of P53 and ATM polymorphisms with risk or radiation-induced pneumonitis in lung cancer patients treated with radiotherapy. Int J Radiat Oncol Biol Phys 2011; 79 (5): 14021407.
153. Jung, I L, Kang, H J, Kim, K C, Kim, I G. PTEN/pAkt/p53 signaling pathway correlates with radioresponse of non-small cell lung cancer. Int J Mol Med 2010; 25: 517523.
154. He, X C, Yin, T, Grindley, J C et al. PTEN-deficient intestinal stem cells initiate intestinal polyposis. Nat Genet 2007; 39: 189198.
155. Bentzen, S M, Heeren, G, Cottier, B et al. Towards evidence-based guidelines for radiotherapy infrastructure and staffing needs in Europe: the ESTRO QUARTS project. Radiother Oncol 2005; 75 (3): 355365.
156. Baumann, M, Petersen, C. TCP and NTCP: a basic introduction. Rays 2005; 30 (2): 99104.
157. Hsu, P D, Lander, E S, Zhang, F. Development and applications of CRISPR-Cas9 for genome engineering. Cell 2014; 157 (6): 12621278.
158. Yap, M L, Zubizarreta, E, Bray, F, Ferlay, J, Barton, M. Global access to radiotherapy services: have we made progress during the past decade? J Glob Oncol 2016; 2 (4): 207–215.



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