REFERENCES
1. Otter SJ, Stewart AJ, Devlin PM. Modern brachytherapy. Hematol Oncol Clin North Am 2019;33:1011-25.
2. Daguenet E, Louati S, Wozny AS, et al. Radiation-induced bystander and abscopal effects: important lessons from preclinical models. Br J Cancer 2020;123:339-48.
3. Halperin EC, Wazer DE, Perez CA, Brady LW. Perez & Brady’s Principles and Practice of Radiation Oncology. Lippincott Williams & Wilkins; 2018. p. 24.
4. Mounier NM, Abdel-Maged AE, Wahdan SA, Gad AM, Azab SS. Chemotherapy-induced cognitive impairment (CICI): An overview of etiology and pathogenesis. Life Sci 2020;258:118071.
5. Delou JMA, Souza ASO, Souza LCM, Borges HL. Highlights in resistance mechanism pathways for combination therapy. Cells 2019;8:1013.
6. Sato K, Shimokawa T, Imai T. Difference in acquired radioresistance induction between repeated photon and particle irradiation. Front Oncol 2019;9:1213.
7. Ali MY, Oliva CR, Noman ASM, et al. Radioresistance in glioblastoma and the development of radiosensitizers. Cancers 2020;12:2511.
8. Zhan Y, Fan S. Multiple mechanisms involving in radioresistance of nasopharyngeal carcinoma. J Cancer 2020;11:4193-204.
9. 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.
10. Karpuz M, Silindir-Gunay M, Ozer AY. Current and future approaches for effective cancer imaging and treatment. Cancer Biother Radiopharm 2018;33:39-51.
11. Ramos P, Bentires-Alj M. Mechanism-based cancer therapy: resistance to therapy, therapy for resistance. Oncogene 2015;34:3617-26.
12. Reisz JA, Bansal N, Qian J, Zhao W, Furdui CM. Effects of ionizing radiation on biological molecules--mechanisms of damage and emerging methods of detection. Antioxid Redox Signal 2014;21:260-92.
13. Zou Z, Chang H, Li H, Wang S. Induction of reactive oxygen species: an emerging approach for cancer therapy. Apoptosis 2017;22:1321-35.
14. Mailloux RJ. An Update on Mitochondrial Reactive Oxygen Species Production. Antioxidants 2020;9:472.
15. Tubbs A, Nussenzweig A. Endogenous DNA damage as a source of genomic instability in cancer. Cell 2017;168:644-56.
16. Vilenchik MM, Knudson AG. Endogenous DNA double-strand breaks: production, fidelity of repair, and induction of cancer. Proc Natl Acad Sci USA 2003;100:12871-6.
17. Mehta A, Haber JE. Sources of DNA double-strand breaks and models of recombinational DNA repair. Cold Spring Harb Perspect Biol 2014;6:a016428.
18. Yang W, Gao Y. Translesion and repair DNA polymerases: diverse structure and mechanism. Annu Rev Biochem 2018;87:239-61.
19. Allen C, Ashley AK, Hromas R, Nickoloff JA. More forks on the road to replication stress recovery. J Mol Cell Biol 2011;3:4-12.
20. Gaillard H, Garcia-Muse T, Aguilera A. Replication stress and cancer. Nat Rev Cancer 2015;15:276-89.
21. Zhang J, Walter JC. Mechanism and regulation of incisions during DNA interstrand cross-link repair. DNA Repair 2014;19:135-42.
22. Shaheen R, Faqeih E, Ansari S, et al. Genomic analysis of primordial dwarfism reveals novel disease genes. Genome Res 2014;24:291-9.
23. Croteau DL, Popuri V, Opresko PL, Bohr VA. Human RecQ helicases in DNA repair, recombination, and replication. Annu Rev Biochem 2014;83:519-52.
24. Casper AM, Durkin SG, Arlt MF, Glover TW. Chromosomal instability at common fragile sites in Seckel syndrome. Am J Hum Genet 2004;75:654-60.
25. Gavande NS, VanderVere-Carozza PS, Hinshaw HD, et al. DNA repair targeted therapy: The past or future of cancer treatment? Pharmacol Ther 2016;160:65-83.
26. Pearl LH, Schierz AC, Ward SE, Al-Lazikani B, Pearl FM. Therapeutic opportunities within the DNA damage response. Nat Rev Cancer 2015;15:166-80.
27. Nickoloff JA. Paths from DNA damage and signaling to genome rearrangements via homologous recombination. Mutat Res 2017;806:64-74.
28. Nickoloff JA, Boss MK, Allen CP, LaRue SM. Translational research in radiation-induced DNA damage signaling and repair. Transl Cancer Res 2017;6:S875-S91.
29. Desai A, Yan Y, Gerson SL. Advances in therapeutic targeting of the DNA damage response in cancer. DNA Repair 2018;66-67:24-9.
30. Blackford AN, Jackson SP. ATM, ATR, and DNA-PK: the trinity at the heart of the DNA damage response. Mol Cell 2017;66:801-17.
31. Hengel SR, Spies MA, Spies M. Small-molecule inhibitors targeting DNA repair and DNA repair deficiency in research and cancer therapy. Cell Chem Biol 2017;24:1101-19.
32. Killock D. Targeted therapies: DNA polymerase theta-a new target for synthetic lethality? Nat Rev Clin Oncol 2015;12:125.
33. Pilie PG, Tang C, Mills GB, Yap TA. State-of-the-art strategies for targeting the DNA damage response in cancer. Nat Rev Clin Oncol 2019;16:81-104.
34. Carrassa L, Damia G. DNA damage response inhibitors: Mechanisms and potential applications in cancer therapy. Cancer Treat Rev 2017;60:139-51.
35. Nickoloff JA, Jones D, Lee S-H, Williamson EA, Hromas R. Drugging the cancers addicted to DNA repair. J Natl Cancer Inst 2017;109:djx059.
36. Yazinski SA, Zou L. Functions, regulation, and therapeutic implications of the ATR checkpoint pathway. Annu Rev Genet 2016;50:155-73.
37. Serrano MA, Li Z, Dangeti M, et al. DNA-PK, ATM and ATR collaboratively regulate p53-RPA interaction to facilitate homologous recombination DNA repair. Oncogene 2013;32:2452-62.
39. Weber AM, Ryan AJ. ATM and ATR as therapeutic targets in cancer. Pharmacol Ther 2015;149:124-38.
40. Williams RM, Yates LA, Zhang X. Structures and regulations of ATM and ATR, master kinases in genome integrity. Curr Opin Struct Biol 2020;61:98-105.
42. Matsuoka S, Ballif BA, Smogorzewska A, et al. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 2007;316:1160-6.
44. Merry C, Fu K, Wang J, Yeh IJ, Zhang Y. Targeting the checkpoint kinase Chk1 in cancer therapy. Cell Cycle 2010;9:279-83.
45. Smith J, Tho LM, Xu N, Gillespie DA. The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res 2010;108:73-112.
46. Mladenov E, Magin S, Soni A, Iliakis G. DNA double-strand-break repair in higher eukaryotes and its role in genomic instability and cancer: Cell cycle and proliferation-dependent regulation. Semin Cancer Biol 2016;37-38:51-64.
47. Berti M, Vindigni A. Replication stress: getting back on track. Nat Struct Mol Biol 2016;23:103-9.
49. Mazouzi A, Velimezi G, Loizou JI. DNA replication stress: causes, resolution and disease. Exp Cell Res 2014;329:85-93.
50. Zeman MK, Cimprich KA. Causes and consequences of replication stress. Nat Cell Biol 2014;16:2-9.
51. Chang HHY, Pannunzio NR, Adachi N, Lieber MR. Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat Rev Mol Cell Biol 2017;18:495-506.
52. Wright WD, Shah SS, Heyer WD. Homologous recombination and the repair of DNA double-strand breaks. J Biol Chem 2018;293:10524-35.
53. de Koning AP, Gu W, Castoe TA, Batzer MA, Pollock DD. Repetitive elements may comprise over two-thirds of the human genome. PLoS Genet 2011;7:e1002384.
54. Piazza A, Heyer WD. Homologous recombination and the formation of complex genomic rearrangements. Trends Cell Biol 2019;29:135-49.
55. Guirouilh-Barbat J, Lambert S, Bertrand P, Lopez BS. Is homologous recombination really an error-free process? Front Genet 2014;5:175.
56. Sfeir A, Symington LS. Microhomology-mediated end joining: a back-up survival mechanism or dedicated pathway? Trends Biochem Sci 2015;40:701-14.
57. Costantino L, Sotiriou SK, Rantala JK, et al. Break-induced replication repair of damaged forks induces genomic duplications in human cells. Science 2014;343:88-91.
58. Iliakis G, Murmann T, Soni A. Alternative end-joining repair pathways are the ultimate backup for abrogated classical non-homologous end-joining and homologous recombination repair: Implications for the formation of chromosome translocations. Mutat Res Genet Toxicol Environ Mutagen 2015;793:166-75.
59. Malkova A, Ira G. Break-induced replication: functions and molecular mechanism. Curr Opin Genet Dev 2013;23:271-9.
60. Sotiriou SK, Kamileri I, Lugli N, et al. Mammalian RAD52 functions in break-induced replication repair of collapsed DNA replication forks. Mol Cell 2016;64:1127-34.
61. Tutt A, Bertwistle D, Valentine J, et al. Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences. EMBO J 2001;20:4704-16.
62. Bhargava R, Onyango DO, Stark JM. Regulation of single-strand annealing and its role in genome maintenance. Trends Genet 2016;32:566-75.
63. Karger CP, Peschke P. RBE and related modeling in carbon-ion therapy. Phys Med Biol 2017;63:01TR02.
64. Nickoloff JA, Sharma N, Taylor L. Clustered DNA double-strand breaks: biological effects and relevance to cancer radiotherapy. Genes 2020;11:99-116.
65. Paganetti H. Relative biological effectiveness (RBE) values for proton beam therapy. Variations as a function of biological endpoint, dose, and linear energy transfer. Phys Med Biol 2014;59:R419-72.
66. Howard M, Beltran C, Sarkaria J, Herman MG. Characterization of relative biological effectiveness for conventional radiation therapy: a comparison of clinical 6 MV X-rays and 137Cs. J Radiat Res 2017;58:608-13.
67. Asaithamby A, Chen DJ. Cellular responses to DNA double-strand breaks after low-dose γ-irradiation. Nucleic Acids Res 2009;37:3912-23.
68. Lomax ME, Folkes LK, O’Neill P. Biological consequences of radiation-induced DNA damage: relevance to radiotherapy. Clin Oncol (R Coll Radiol) 2013;25:578-85.
69. Vitti ET, Parsons JL. The radiobiological effects of proton beam therapy: impact on DNA damage and repair. Cancers 2019;11:946.
70. Nickoloff JA. Photon, light ion, and heavy ion cancer radiotherapy: paths from physics and biology to clinical practice. Ann Transl Med 2015;3:336.
71. Bukowska B, Karwowski BT. The clustered DNA lesions - types, pathways of repair and relevance to human health. Curr Med Chem 2018;25:2722-35.
72. Mladenova V, Mladenov E, Iliakis G. Novel biological approaches for testing the contributions of single DSBs and DSB clusters to the biological effects of high LET radiation. Front Oncol 2016;6:163.
73. Sage E, Shikazono N. Radiation-induced clustered DNA lesions: Repair and mutagenesis. Free Radic Biol Med 2017;107:125-35.
74. Pang D, Winters TA, Jung M, et al. Radiation-generated short DNA fragments may perturb non-homologous end-joining and induce genomic instability. J Radiat Res 2011;52:309-19.
75. Chan DW, Chen BP-C, Prithivirasingh S, et al. Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Genes Dev 2002;16:2333-8.
76. Okayasu R, Okada M, Okabe A, et al. Repair of DNA damage induced by accelerated heavy ions in mammalian cells proficient and deficient in the non-homologous end-joining pathway. Radiat Res 2006;165:59-67.
77. Wang H, Zhang X, Wang P, et al. Characteristics of DNA-binding proteins determine the biological sensitivity to high-linear energy transfer radiation. Nucleic Acids Res 2010;38:3245-51.
78. Hada M, Sutherland BM. Spectrum of complex DNA damages depends on the incident radiation. Radiat Res 2006;165:223-30.
79. Gerelchuluun A, Manabe E, Ishikawa T, et al. The major DNA repair pathway after both proton and carbon-ion radiation is NHEJ, but the HR pathway is more relevant in carbon ions. Radiat Res 2015;183:345-56.
80. Fontana AO, Augsburger MA, Grosse N, et al. Differential DNA repair pathway choice in cancer cells after proton- and photon-irradiation. Radiother Oncol 2015;116:374-80.
81. Vitti ET, Kacperek A, Parsons JL. Targeting DNA double-strand break repair enhances radiosensitivity of HPV-positive and HPV-negative head and neck squamous cell carcinoma to photons and protons. Cancers 2020;12:1490.
82. Cartwright IM, Su C, Haskins JS, et al. DNA repair deficient chinese hamster ovary cells exhibiting differential sensitivity to charged particle radiation under aerobic and hypoxic conditions. Int J Mol Sci 2018;19:2228.
83. Antonovic L, Lindblom E, Dasu A, et al. Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes. J Radiat Res 2014;55:902-11.
84. Pawlik TM, Keyomarsi K. Role of cell cycle in mediating sensitivity to radiotherapy. Int J Radiat Oncol Biol Phys 2004;59:928-42.
85. Higgins PD, DeLuca PM Jr., Gould MN. Effect of pulsed dose in simultaneous and sequential irradiation of V-79 cells by 14.8-MeV neutrons and 60Co photons. Radiat Res 1984;99:591-5.
86. Cheng L, Brzozowska B, Sollazzo A, et al. Simultaneous induction of dispersed and clustered DNA lesions compromises DNA damage response in human peripheral blood lymphocytes. PLoS One 2018;13:e0204068.
87. Staaf E, Brehwens K, Haghdoost S, Czub J, Wojcik A. Gamma-H2AX foci in cells exposed to a mixed beam of X-rays and alpha particles. Genome Integr 2012;3:8.
88. Newhauser WD, Durante M. Assessing the risk of second malignancies after modern radiotherapy. Nat Rev Cancer 2011;11:438-48.
89. Tsujii H, Kamada T, Shirai T, et al. Carbon-Ion Radiotherapy Principals, Practices, and Treatment Planning. Tokyo: Springer; 2014. p. 312.
90. Tsujii H, Kamada T. A review of update clinical results of carbon ion radiotherapy. Jpn J Clin Oncol 2012;42:670-85.
91. Kamada T, Tsujii H, Blakely EA, et al. Carbon ion radiotherapy in Japan: an assessment of 20 years of clinical experience. Lancet Oncol 2015;16:e93-e100.
92. Allen CP, Borak TB, Tsujii H, Nickoloff JA. Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy. Mutat Res 2011;711:150-7.
93. Sunada S, Cartwright IM, Hirakawa H, et al. Investigation of the relative biological effectiveness and uniform isobiological killing effects of irradiation with a clinical carbon SOBP beam on DNA repair deficient CHO cells. Oncol Lett 2017;13:4911-6.
94. Buglewicz DJ, Banks AB, Hirakawa H, Fujimori A, Kato TA. Monoenergetic 290 MeV/n carbon-ion beam biological lethal dose distribution surrounding the Bragg peak. Sci Rep 2019;9:6157.
95. Kato TA, Wilson PF, Nagasaw H, et al. Variations in radiosensitivity among individuals: a potential impact on risk assessment? Health Phys 2009;97:470-80.
96. Wilson PF, Nagasawa H, Fitzek MM, Little JB, Bedford JS. G2-phase chromosomal radiosensitivity of primary fibroblasts from hereditary retinoblastoma family members and some apparently normal controls. Radiat Res 2010;173:62-70.
97. Kirsch DG. Current opportunities and future vision of precision medicine in radiation oncology. Int J Radiat Oncol Biol Phys 2018;101:267-70.
98. Speers C, Zhao S, Liu M, et al. Development and validation of a novel radiosensitivity signature in human breast cancer. Clin Cancer Res 2015;21:3667-77.
99. Willers H, Azzoli CG, Santivasi WL, Xia F. Basic mechanisms of therapeutic resistance to radiation and chemotherapy in lung cancer. Cancer J 2013;19:200-7.
100. Hill RP, Bristow RG, Fyles A, et al. Hypoxia and predicting radiation response. Semin Radiat Oncol 2015;25:260-72.
101. Kim BM, Hong Y, Lee S, et al. Therapeutic implications for overcoming radiation resistance in cancer therapy. Int J Mol Sci 2015;16:26880-913.
102. Hu J, Li H, Luo X, et al. The role of oxidative stress in EBV lytic reactivation, radioresistance and the potential preventive and therapeutic implications. Int J Cancer 2017;141:1722-9.
103. Wardman P. Nitroimidazoles as hypoxic cell radiosensitizers and hypoxia probes: misonidazole, myths and mistakes. Br J Radiol 2019;92:20170915.
104. Bonnet M, Hong CR, Wong WW, et al. Next-generation hypoxic cell radiosensitizers: nitroimidazole alkylsulfonamides. J Med Chem 2018;61:1241-54.
105. Olivares-Urbano MA, Grinan-Lison C, Marchal JA, Nunez MI. CSC radioresistance: a therapeutic challenge to improve radiotherapy effectiveness in cancer. Cells 2020;9:1651.
106. Liu Y, Yang M, Luo J, Zhou H. Radiotherapy targeting cancer stem cells “awakens” them to induce tumour relapse and metastasis in oral cancer. Int J Oral Sci 2020;12:19.
107. Schulz A, Meyer F, Dubrovska A, Borgmann K. Cancer stem cells and radioresistance: DNA repair and beyond. Cancers 2019;11:862.
108. Talukdar S, Bhoopathi P, Emdad L, et al. Dormancy and cancer stem cells: An enigma for cancer therapeutic targeting. Adv Cancer Res 2019;141:43-84.
109. Peeken JC, Vaupel P, Combs SE. Integrating hyperthermia into modern radiation oncology: What evidence Is necessary? Front Oncol 2017;7:132.
110. Oei AL, Vriend LE, Crezee J, Franken NA, Krawczyk PM. Effects of hyperthermia on DNA repair pathways: one treatment to inhibit them all. Radiat Oncol 2015;10:165.
111. Genet SC, Fujii Y, Maeda J, et al. Hyperthermia inhibits homologous recombination repair and sensitizes cells to ionizing radiation in a time- and temperature-dependent manner. J Cell Physiol 2013;228:1473-81.
112. Zhu L, Altman MB, Laszlo A, et al. Ultrasound hyperthermia technology for radiosensitization. Ultrasound Med Biol 2019;45:1025-43.
113. Lewis JE, Singh N, Holmila RJ, et al. Targeting NAD+ Metabolism to Enhance Radiation Therapy Responses. Semin Radiat Oncol 2019;29:6-15.
114. Ashcraft KA, Warner AB, Jones LW, Dewhirst MW. Exercise as adjunct therapy in cancer. Semin Radiat Oncol 2019;29:16-24.
115. Schoenfeld JD, Alexander MS, Waldron TJ, et al. Pharmacological ascorbate as a means of sensitizing cancer cells to radio-chemotherapy while protecting normal tissue. Semin Radiat Oncol 2019;29:25-32.
116. Floberg JM, Schwarz JK. Manipulation of glucose and hydroperoxide metabolism to improve radiation response. Semin Radiat Oncol 2019;29:33-41.
117. Aykin-Burns N, Pathak R, Boerma M, Kim T, Hauer-Jensen M. Utilization of vitamin E analogs to protect normal tissues while enhancing antitumor effects. Semin Radiat Oncol 2019;29:55-61.
118. Hillman GG. Soy isoflavones protect normal tissues while enhancing radiation responses. Semin Radiat Oncol 2019;29:62-71.
119. Boss MK, Deegan R, Batinic-Haberle I, et al. Manganese porphyrin and radiotherapy improves local tumor response and overall survival in orthotopic murine mammary carcinoma models. Radiat Res 2020. (in press)
120. Mortezaee K, Shabeeb D, Musa AE, Najafi M, Farhood B. Metformin as a radiation modifier; implications to normal tissue protection and tumor sensitization. Curr Clin Pharmacol 2019;14:41-53.
121. Lin A, Maity A. Molecular pathways: A novel approach to targeting hypoxia and improving radiotherapy efficacy via reduction in oxygen demand. Clin Cancer Res 2015;21:1995-2000.
122. Fernandes JM, Jandrey EHF, Koyama FC, et al. Metformin as an alternative radiosensitizing agent to 5FU during neoadjuvant treatment for rectal cancer. Dis Colon Rectum 2020;63:918-26.
123. Farhood B, Goradel NH, Mortezaee K, et al. Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization. Clin Transl Oncol 2019;21:268-79.
125. Livingston K, Schlaak RA, Puckett LL, Bergom C. The role of mitochondrial dysfunction in radiation-induced heart disease: from bench to bedside. Front Cardiovasc Med 2020;7:20.
126. Thermozier S, Hou W, Zhang X, et al. Anti-ferroptosis drug enhances total-body irradiation mitigation by drugs that block apoptosis and necroptosis. Radiat Res 2020;193:435-50.
127. Olivieri G, Bodycote J, Wolff S. Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. Science 1984;223:594-7.
128. Huang L, Kim PM, Nickoloff JA, Morgan WF. Targeted and non-targeted effects of low-dose ionizing radiation on delayed genomic instability in human cells. Cancer Res 2007;67:1099-104.
129. Ikushima T. Radio-adaptive response: characterization of a cytogenetic repair induced by low-level ionizing radiation in cultured Chinese hamster cells. Mutat Res 1989;227:241-6.
130. Rigaud O, Moustacchi E. Radioadaptation for gene mutation and the possible molecular mechanisms of the adaptive response. Mutat Res 1996;358:127-34.
131. Redpath JL, Antoniono RJ. Induction of an adaptive response against spontaneous neoplastic transformation in vitro by low-dose gamma radiation. Radiat Res 1998;149:517-20.
132. Barquinero JF, Barrios L, Caballin MR, et al. Occupational exposure to radiation induces an adaptive response in human lymphocytes. Int J Radiat Biol 1995;67:187-91.
133. Monsieurs MA, Thierens HM, Vral AM, et al. Adaptive response in patients treated with 131I. J Nucl Med 2000;41:17-22.
134. Grdina DJ, Murley JS, Miller RC, et al. A survivin-associated adaptive response in radiation therapy. Cancer Res 2013;73:4418-28.
135. Grdina DJ, Murley JS, Miller RC, et al. A manganese superoxide dismutase (SOD2)-mediated adaptive response. Radiat Res 2013;179:115-24.
136. Grdina DJ, Murley JS, Miller RC, Woloschak GE, Li JJ. NFkappaB and survivin-mediated radio-adaptive response. Radiat Res 2015;183:391-7.
137. Murley JS, Miller RC, Weichselbaum RR, Grdina DJ. TP53 mutational status and ROS effect the expression of the survivin-associated radio-adaptive response. Radiat Res 2017;188:579-90.
138. Murley JS, Arbiser JL, Weichselbaum RR, Grdina DJ. ROS modifiers and NOX4 affect the expression of the survivin-associated radio-adaptive response. Free Radic Biol Med 2018;123:39-52.
139. Unruhe B, Schroder E, Wunsch D, Knauer SK. An old flame never dies: Survivin in cancer and cellular senescence. Gerontology 2016;62:173-81.
140. Coleman CN, Eke I, Makinde AY, et al. Radiation-induced adaptive response: new potential for cancer treatment. Clin Cancer Res 2020;26:5781-90.
141. Sato H, Niimi A, Yasuhara T, et al. DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells. Nat Commun 2017;8:1751.
143. Russo M, Crisafulli G, Sogari A, et al. Adaptive mutability of colorectal cancers in response to targeted therapies. Science 2019;366:1473-80.
144. Scott JG, Berglund A, Schell MJ, et al. A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study. Lancet Oncol 2017;18:202-11.
145. Trenner A, Sartori AA. Harnessing DNA double-strand break repair for cancer treatment. Front Oncol 2019;9:1388.
146. Kirsch DG, Diehn M, Kesarwala AH, et al. The future of radiobiology. J Natl Cancer Inst 2018;110:329-40.
147. Kelley MR, Logsdon D, Fishel ML. Targeting DNA repair pathways for cancer treatment: what’s new? Future Oncol 2014;10:1215-37.
148. Toulany M. Targeting DNA double-strand break repair pathways to improve radiotherapy response. Genes 2019;10:25.
149. Mohiuddin IS, Kang MH. DNA-PK as an emerging therapeutic target in cancer. Front Oncol 2019;9:635.
150. Dong J, Ren Y, Zhang T, et al. Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair. Oncol Rep 2018;39:912-20.
151. Yang C, Wang Q, Liu X, et al. NU7441 enhances the radiosensitivity of liver cancer cells. Cell Physiol Biochem 2016;38:1897-905.
152. Sunada S, Kanai H, Lee Y, et al. Nontoxic concentration of DNA-PK inhibitor NU7441 radio-sensitizes lung tumor cells with little effect on double strand break repair. Cancer Sci 2016;107:1250-5.
153. Timme CR, Rath BH, O’Neill JW, Camphausen K, Tofilon PJ. The DNA-PK inhibitor VX-984 enhances the radiosensitivity of glioblastoma cells grown in vitro and as orthotopic xenografts. Mol Cancer Ther 2018;17:1207-16.
154. Willoughby CE, Jiang Y, Thomas HD, et al. Selective DNA-PKcs inhibition extends the therapeutic index of localized radiotherapy and chemotherapy. J Clin Invest 2020;130:258-71.
155. Smith MC, Mader MM, Cook JA, et al. Characterization of LY3023414, a vovel PI3K/mTOR dual inhibitor eliciting transient target modulation to impede tumor growth. Mol Cancer Ther 2016;15:2344-56.
156. Tsuji T, Sapinoso LM, Tran T, et al. CC-115, a dual inhibitor of mTOR kinase and DNA-PK, blocks DNA damage repair pathways and selectively inhibits ATM-deficient cell growth in vitro. Oncotarget 2017;8:74688-702.
157. Lindquist KE, Cran JD, Kordic K, et al. Selective radiosensitization of hypoxic cells using BCCA621C: a novel hypoxia activated prodrug targeting DNA-dependent protein kinase. Tumour Microenv Ther 2013;1:46-55.
158. Dittmann K, Mayer C, Rodemann HP. Inhibition of radiation-induced EGFR nuclear import by C225 (Cetuximab) suppresses DNA-PK activity. Radiother Oncol 2005;76:157-61.
159. Joseph K, Alkaabi K, Warkentin H, et al. Cetuximab-radiotherapy combination in the management of locally advanced cutaneous squamous cell carcinoma. J Med Imaging Radiat Oncol 2019;63:257-63.
160. Qi Y, Lang J, Zhu X, et al. Down-regulation of the radiation-induced pEGFRThr654 mediated activation of DNA-PK by Cetuximab in cervical cancer cells. RSC Adv 2020;10:1132-41.
161. Balbous A, Cortes U, Guilloteau K, et al. A radiosensitizing effect of RAD51 inhibition in glioblastoma stem-like cells. BMC Cancer 2016;16:604.
162. King HO, Brend T, Payne HL, et al. RAD51 Is a selective DNA repair target to radiosensitize glioma stem cells. Stem Cell Reports 2017;8:125-39.
163. Pastushok L, Fu Y, Lin L, et al. A novel cell-penetrating antibody fragment inhibits the DNA repair protein RAD51. Sci Rep 2019;9:11227.
164. Turchick A, Liu Y, Zhao W, Cohen I, Glazer PM. Synthetic lethality of a cell-penetrating anti-RAD51 antibody in PTEN-deficient melanoma and glioma cells. Oncotarget 2019;10:1272-83.
165. Turchick A, Hegan DC, Jensen RB, Glazer PM. A cell-penetrating antibody inhibits human RAD51 via direct binding. Nucleic Acids Res 2017;45:11782-99.
166. Cyteir Therapeutics I. A phase 1/2 study of CYT-0851, an oral RAD51 inhibitor, in B-cell malignancies and advanced solid tumors. In; 2019.
167. Yu D, Sekine E, Fujimori A, Ochiya T, Okayasu R. Down regulation of BRCA2 causes radio-sensitization of human tumor cells in vitro and in vivo. Cancer Sci 2008;99:810-5.
168. Hirai T, Shirai H, Fujimori H, et al. Radiosensitization effect of poly(ADP-ribose) polymerase inhibition in cells exposed to low and high linear energy transfer radiation. Cancer Sci 2012;103:1045-50.
169. Hirai T, Saito S, Fujimori H, et al. Radiosensitization by PARP inhibition to proton beam irradiation in cancer cells. Biochem Biophys Res Commun 2016;478:234-40.
170. Jannetti SA, Zeglis BM, Zalutsky MR, Reiner T. Poly(ADP-ribose)polymerase (PARP) inhibitors and radiation therapy. Front Pharmacol 2020;11:170.
171. Chang L, Graham PH, Hao J, et al. PI3K/Akt/mTOR pathway inhibitors enhance radiosensitivity in radioresistant prostate cancer cells through inducing apoptosis, reducing autophagy, suppressing NHEJ and HR repair pathways. Cell Death Dis 2014;5:e1437.
172. Schotz U, Balzer V, Brandt FW, et al. Dual PI3K/mTOR inhibitor NVP-BEZ235 enhances radiosensitivity of head and neck squamous cell carcinoma (HNSCC) cell lines due to suppressed double-strand break (DSB) repair by non-homologous end joining. Cancers 2020;12:467.
173. Gil del Alcazar CR, Hardebeck MC, Mukherjee B, et al. Inhibition of DNA double-strand break repair by the dual PI3K/mTOR inhibitor NVP-BEZ235 as a strategy for radiosensitization of glioblastoma. Clin Cancer Res 2014;20:1235-48.
174. Hirakawa H, Fujisawa H, Masaoka A, et al. The combination of Hsp90 inhibitor 17AAG and heavy-ion irradiation provides effective tumor control in human lung cancer cells. Cancer Med 2015;4:426-36.
175. Lee Y, Li HK, Masaoka A, et al. The purine scaffold Hsp90 inhibitor PU-H71 sensitizes cancer cells to heavy ion radiation by inhibiting DNA repair by homologous recombination and non-homologous end joining. Radiother Oncol 2016;121:162-8.
176. Noguchi M, Yu D, Hirayama R, et al. Inhibition of homologous recombination repair in irradiated tumor cells pretreated with Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin. Biochem Biophys Res Commun 2006;351:658-63.
177. Segawa T, Fujii Y, Tanaka A, et al. Radiosensitization of human lung cancer cells by the novel purine-scaffold Hsp90 inhibitor, PU-H71. Int J Mol Med 2014;33:559-64.
178. Lee Y, Sunada S, Hirakawa H, et al. TAS-116, a novel Hsp90 inhibitor, selectively enhances radiosensitivity of human cancer cells to X-rays and carbon ion radiation. Mol Cancer Ther 2017;16:16-24.
179. Fujii Y, Kato T, Kubota N, et al. p53 independent radio-sensitization of human lymphoblastoid cell lines by Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin. Oncol Rep 2010;23:199-203.
180. Shimomura A, Yamamoto N, Kondo S, et al. First-in-human Phase I study of an oral HSP90 inhibitor, TAS-116, in patients with advanced solid tumors. Mol Cancer Ther 2019;18:531-40.
181. Vormoor B, Schlosser YT, Blair H, et al. Sensitizing Ewing sarcoma to chemo- and radiotherapy by inhibition of the DNA-repair enzymes DNA protein kinase (DNA-PK) and poly-ADP-ribose polymerase (PARP) 1/2. Oncotarget 2017;8:113418-30.
182. Fok JHL, Ramos-Montoya A, Vazquez-Chantada M, et al. AZD7648 is a potent and selective DNA-PK inhibitor that enhances radiation, chemotherapy and olaparib activity. Nat Commun 2019;10:5065.
183. Zhang Q, Green MD, Lang X, et al. Inhibition of ATM increases interferon signaling and sensitizes pancreatic cancer to immune checkpoint blockade therapy. Cancer Res 2019;79:3940-51.
184. Chen BP, Uematsu N, Kobayashi J, et al. Ataxia telangiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at the Thr-2609 cluster upon DNA double strand break. J Biol Chem 2007;282:6582-7.
185. Cornell L, Munck JM, Alsinet C, et al. DNA-PK-A candidate driver of hepatocarcinogenesis and tissue biomarker that predicts response to treatment and survival. Clin Cancer Res 2015;21:925-33.
186. Abdel-Fatah TM, Arora A, Moseley P, et al. ATM, ATR and DNA-PKcs expressions correlate to adverse clinical outcomes in epithelial ovarian cancers. BBA Clin 2014;2:10-7.
187. Toulany M, Maier J, Iida M, et al. Akt1 and Akt3 but not Akt2 through interaction with DNA-PKcs stimulate proliferation and post-irradiation cell survival of K-RAS-mutated cancer cells. Cell Death Discov 2017;3:17072.
188. Baptistella AR, Landemberger MC, Dias MVS, et al. Rab5C enhances resistance to ionizing radiation in rectal cancer. J Mol Med 2019;97:855-69.
189. Zou M, Li Y, Xia S, et al. Knockdown of CAVEOLIN-1 sensitizes human basal-like triple-negative breast cancer cells to radiation. Cell Physiol Biochem 2017;44:778-91.
190. Saki M, Makino H, Javvadi P, et al. EGFR mutations compromise hypoxia-associated radiation resistance through impaired replication fork-associated DNA damage repair. Mol Cancer Res 2017;15:1503-16.
191. Amunugama R, Fishel R. Homologous recombination in eukaryotes. Prog Mol Biol Transl Sci 2012;110:155-206.
192. Shrivastav M, Miller CA, De Haro LP, et al. DNA-PKcs and ATM co-regulate DNA double-strand break repair. DNA Repair 2009;8:920-9.
193. Nickoloff JA, Brenneman MA. Analysis of recombinational repair of DNA double-strand breaks in mammalian cells with I-SceI nuclease. Methods Mol Biol 2004;262:35-52.
194. Yoshino Y, Endo S, Chen Z, et al. Evaluation of site-specific homologous recombination activity of BRCA1 by direct quantitation of gene editing efficiency. Sci Rep 2019;9:1644.
195. Price BD, D’Andrea AD. Chromatin remodeling at DNA double-strand breaks. Cell 2013;152:1344-54.
196. Kaushal S, Freudenreich CH. The role of fork stalling and DNA structures in causing chromosome fragility. Genes Chromosomes Cancer 2019;58:270-83.
197. Wray J, Liu J, Nickoloff JA, Shen Z. Distinct RAD51 associations with RAD52 and BCCIP in response to DNA damage and replication stress. Cancer Res 2008;68:2699-707.
198. Groth P, Orta ML, Elvers I, et al. Homologous recombination repairs secondary replication induced DNA double-strand breaks after ionizing radiation. Nucleic Acids Res 2012;40:6585-94.
200. Budke B, Logan HL, Kalin JH, et al. RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells. Nucleic Acids Res 2012;40:7347-57.
201. Budke B, Lv W, Kozikowski AP, Connell PP. Recent developments using small molecules to target RAD51: How to best modulate RAD51 for anticancer therapy? ChemMedChem 2016;11:2468-73.
202. Lv W, Budke B, Pawlowski M, Connell PP, Kozikowski AP. Development of small molecules that specifically inhibit the D-loop activity of RAD51. J Med Chem 2016;59:4511-25.
203. Mersch J, Jackson MA, Park M, et al. Cancers associated with BRCA1 and BRCA2 mutations other than breast and ovarian. Cancer 2015;121:269-75.
204. Sekhar D, Pooja S, Kumar S, Rajender S. RAD51 135G > C substitution increases breast cancer risk in an ethnic-specific manner: a meta-analysis on 21,236 cases and 19,407 controls. Sci Rep 2015;5:11588.
206. Jette NR, Kumar M, Radhamani S, et al. ATM-deficient cancers provide new opportunities for precision oncology. Cancers 2020;12:687.
207. Byrum AK, Vindigni A, Mosammaparast N. Defining and modulating ‘BRCAness’. Trends Cell Biol 2019;29:740-51.
208. Pommier Y, O’Connor MJ, de Bono J. Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action. Sci Transl Med 2016;8:362ps17.
209. Yi M, Dong B, Qin S, et al. Advances and perspectives of PARP inhibitors. Exp Hematol Oncol 2019;8:29.
210. del Rivero J, Kohn EC. PARP inhibitors: the cornerstone of DNA repair-targeted therapies. Oncology 2017;31:265-73.
211. Gil Del Alcazar CR, Todorova PK, Habib AA, Mukherjee B, Burma S. Augmented HR repair mediates acquired temozolomide resistance in glioblastoma. Mol Cancer Res 2016;14:928-40.
212. Zhang X, Ma N, Yao W, Li S, Ren Z. RAD51 is a potential marker for prognosis and regulates cell proliferation in pancreatic cancer. Cancer Cell Int 2019;19:356.
213. Liu X, Han EK, Anderson M, et al. Acquired resistance to combination treatment with temozolomide and ABT-888 is mediated by both base excision repair and homologous recombination DNA repair pathways. Mol Cancer Res 2009;7:1686-92.
214. Noordermeer SM, van Attikum H. PARP inhibitor resistance: a tug-of-war in BRCA-mutated cells. Trends Cell Biol 2019;29:820-34.
215. D’Andrea AD. Mechanisms of PARP inhibitor sensitivity and resistance. DNA Repair 2018;71:172-6.
216. Tian H, Gao Z, Li H, et al. DNA damage response--a double-edged sword in cancer prevention and cancer therapy. Cancer Lett 2015;358:8-16.
217. Bakr A, Oing C, Kocher S, et al. Involvement of ATM in homologous recombination after end resection and RAD51 nucleofilament formation. Nucleic Acids Res 2015;43:3154-66.
218. Ahlskog JK, Larsen BD, Achanta K, Sorensen CS. ATM/ATR-mediated phosphorylation of PALB2 promotes RAD51 function. EMBO Rep 2016;17:671-81.
220. Glorieux M, Dok R, Nuyts S. Novel DNA targeted therapies for head and neck cancers: clinical potential and biomarkers. Oncotarget 2017;8:81662-78.
221. Riches LC, Trinidad AG, Hughes G, et al. Pharmacology of the ATM inhibitor AZD0156: potentiation of irradiation and olaparib responses preclinically. Mol Cancer Ther 2020;19:13-25.
222. Zhou C, Parsons JL. The radiobiology of HPV-positive and HPV-negative head and neck squamous cell carcinoma. Expert Rev Mol Med 2020;22:e3.
223. Ferri A, Stagni V, Barila D. Targeting the DNA damage response to overcome cancer drug resistance in glioblastoma. Int J Mol Sci 2020;21:4910.
224. Philip CA, Laskov I, Beauchamp MC, et al. Inhibition of PI3K-AKT-mTOR pathway sensitizes endometrial cancer cell lines to PARP inhibitors. BMC Cancer 2017;17:638.
225. Wang D, Li C, Zhang Y, et al. Combined inhibition of PI3K and PARP is effective in the treatment of ovarian cancer cells with wild-type PIK3CA genes. Gynecol Oncol 2016;142:548-56.
226. Cossar LH, Schache AG, Risk JM, et al. Modulating the DNA damage response to improve treatment response in cervical cancer. Clin Oncol 2017;29:626-34.
227. Weitzman MD, Fradet-Turcotte A. Virus DNA replication and the host DNA damage response. Annu Rev Virol 2018;5:141-64.
228. Jafari A, Rezaei-Tavirani M, Farhadihosseinabadi B, Taranejoo S, Zali H. HSP90 and co-chaperones: impact on tumor progression and prospects for molecular-targeted cancer therapy. Cancer Invest 2020;38:310-28.
229. Garcia-Carbonero R, Carnero A, Paz-Ares L. Inhibition of HSP90 molecular chaperones: moving into the clinic. Lancet Oncol 2013;14:e358-69.
230. Jhaveri K, Modi S. HSP90 inhibitors for cancer therapy and overcoming drug resistance. Adv Pharmacol 2012;65:471-517.
231. Kamal A, Thao L, Sensintaffar J, et al. A high-affinity conformation of Hsp90 confers tumour selectivity on Hsp90 inhibitors. Nature 2003;425:407-10.
232. Moulick K, Ahn JH, Zong H, et al. Affinity-based proteomics reveal cancer-specific networks coordinated by Hsp90. Nat Chem Biol 2011;7:818-26.
233. Sessa C, Shapiro GI, Bhalla KN, et al. First-in-human phase I dose-escalation study of the HSP90 inhibitor AUY922 in patients with advanced solid tumors. Clin Cancer Res 2013;19:3671-80.
234. Renouf DJ, Velazquez-Martin JP, Simpson R, Siu LL, Bedard PL. Ocular toxicity of targeted therapies. J Clin Oncol 2012;30:3277-86.
235. Balmus G, Pilger D, Coates J, et al. ATM orchestrates the DNA-damage response to counter toxic non-homologous end-joining at broken replication forks. Nat Commun 2019;10:87.
236. Nickoloff JA. Improving cancer therapy by combining cell biological, physical, and molecular targeting strategies. Chin J Cancer Res 2013;25:7-9.
237. Kon T, Zhang X, Huang Q, et al. Oncolytic virus-mediated tumor radiosensitization in mice through DNA-PKcs-specific shRNA. Transl Cancer Res 2012;1:4-14.
238. Guo P, Yang J, Jia D, Moses MA, Auguste DT. ICAM-1-targeted, Lcn2 siRNA-encapsulating liposomes are potent anti-angiogenic agents for triple negative breast cancer. Theranostics 2016;6:1-13.
