Skip to main content

Advertisement

SpringerLink
Log in

DNA as the main target in radiotherapy—a historical overview from first isolation to anti-tumour immune response

  • Review Article
  • Published:
Strahlentherapie und Onkologie Aims and scope Submit manuscript

Abstract

DNA damage is one of the foremost mechanisms of irradiation at the biological level. After the first isolation of DNA by Friedrich Miescher in the 19th century, the structure of DNA was described by Watson and Crick. Several Nobel Prizes have been awarded for DNA-related discoveries. This review aims to describe the historical perspective of DNA in radiation biology. Over the decades, DNA damage has been identified and quantified after irradiation. Depending on the type of sensing, different proteins are involved in sensing DNA damage and repairing the damage, if possible. For double-strand breaks, the main repair mechanisms are non-homologous end joining and homologous recombination. Additional mechanisms are the Fanconi anaemia pathway and base excision repair. Different methods have been developed for the detection of DNA double-strand breaks. Several drugs have been developed that interfere with different DNA repair mechanisms, e.g., PARP inhibitors. These drugs have been established in the standard treatment of different tumour entities and are being applied in several clinical trials in combination with radiotherapy. Over the past decades, it has become apparent that DNA damage mechanisms are also directly linked to the immune response in tumours. For example, cytosolic DNA fragments activate the innate immune system via the cGAS STING pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Streffer C, Herrmannn T (2012) A century of development in radiation biology. Basic principles of targeted and efficient radiotherapy. Strahlenther Onkol 188(Suppl 3):231–244

    Article  PubMed  Google Scholar 

  2. Suwa T et al (2021) Tumor microenvironment and radioresistance. Exp Mol Med 53(6):1029–1035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kirsch DG et al (2018) The Future of Radiobiology. J Natl Cancer Inst 110(4):329–340

    Article  CAS  PubMed  Google Scholar 

  4. Mavragani IV et al (2016) Key mechanisms involved in ionizing radiation-induced systemic effects. A current review. Toxicol Res (camb) 5(1):12–33

    Article  PubMed  Google Scholar 

  5. Gaipl US et al (2014) Kill and spread the word: stimulation of antitumor immune responses in the context of radiotherapy. Immunotherapy 6(5):597–610

    Article  CAS  PubMed  Google Scholar 

  6. Abuodeh Y, Venkat P, Kim S (2016) Systematic review of case reports on the abscopal effect. Curr Probl Cancer 40(1):25–37

    Article  PubMed  Google Scholar 

  7. Veigl SJ, Harman O, Lamm E (2020) Friedrich Miescher’s Discovery in the Historiography of Genetics: From Contamination to Confusion, from Nuclein to DNA. J Hist Biol 53(3):451–484

    Article  PubMed  Google Scholar 

  8. Dahm R, Discovering DNA (2008) Friedrich Miescher and the early years of nucleic acid research. Hum Genet 122(6):565–581

    Article  CAS  PubMed  Google Scholar 

  9. Boveri T (2008) Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris. J Cell Sci 121(Suppl 1: p):1–84

    Article  PubMed  Google Scholar 

  10. Gager CS, Blakeslee AF (1927) Chromosome and Gene Mutations in Datura Following Exposure to Radium Rays. Proc Natl Acad Sci U S A 13(2):75–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cobb M, Avery ODNA (2014) and the transformation of biology. Curr Biol 24(2):R55–r60

    Article  CAS  PubMed  Google Scholar 

  12. Muller HJ (1699) Artificial Transmutation of the Gene. Science p:84–87

  13. Muller HJ (1928) The Production of Mutations by X‑Rays. Proc Natl Acad Sci U S A 14(9):714–726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Friedberg EC, Wilkins M (2004) 1916–2004. Mol Cell 16(5):671–672

    Article  CAS  PubMed  Google Scholar 

  15. Watson JD, Crick FH (1953) Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 171(4356):737–738

    Article  CAS  PubMed  Google Scholar 

  16. Watson JD, Crick FH (1953) Genetical implications of the structure of deoxyribonucleic acid. Nature 171(4361):964–967

    Article  CAS  PubMed  Google Scholar 

  17. Teive HA (2016) On the centenary of the birth of Francis H. C. Crick—from physics to genetics and neuroscience. Arq Neuropsiquiatr 74(4):351–353

    Article  PubMed  Google Scholar 

  18. Watson JD (2007) Die Doppelhelix, 20th ed edn. Rowohlt, Hamburg

    Google Scholar 

  19. Schuster RC (1964) Dark Repair Of Ultraviolet Injury In E. Coli During Deprivation Of Thymine. Nature 202: p:614–615

    Article  Google Scholar 

  20. Nobel Prizes for Medicine, 1968. Nature, 1968. 220(5165):324–325

  21. Chiche JD, Cariou A, Mira JP (2002) Bench-to-bedside review: fulfilling promises of the Human Genome Project. Crit Care 6(3):212–215

    Article  PubMed  PubMed Central  Google Scholar 

  22. Tompkins JD (2022) Discovering DNA Methylation, the History and Future of the Writing on DNA. J Hist Biol 55(4):865–887. https://doi.org/10.1007/s10739-022-09691-8

  23. Lindahl T, Modrich P, Sancar AT (2016) 2015 Nobel Prize in Chemistry The Discovery of Essential Mechanisms that Repair DNA Damage. J Assoc Genet Technol 42(1):37–41

    PubMed  Google Scholar 

  24. Li C et al (2021) CRISPR/Cas: a Nobel Prize award-winning precise genome editing technology for gene therapy and crop improvement. J Zhejiang Univ Sci B 22(4):253–284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) Molecular Biology of the Cell vol 4th edition. Garland Science, New York. https://doi.org/10.1002/bmb.2003.494031049999

    Google Scholar 

  26. DNA Damage Tolerance and Mutagenesis in Eukaryotic Cells, in DNA Repair and Mutagenesis. 2005. p. 613–661. https://doi.org/10.1128/9781555816704

  27. Martin CL, Warburton D (2015) Detection of Chromosomal Aberrations in Clinical Practice: From Karyotype to Genome Sequence. Annu Rev Genomics Hum Genet 16: p:309–326

    Article  Google Scholar 

  28. Krylov V, Tlapakova T (2015) Xenopus Cytogenetics and Chromosomal Evolution. Cytogenet Genome Res 145(3–4):192–200

    Article  PubMed  Google Scholar 

  29. Streffer C (1980) Biologische Grundlagen der Strahlentherapie. In: Scherer E (ed) Strahlentherapie: Radiologische Onkologie. Springer Berlin Heidelberg, Berlin, Heidelberg, pp 197–266

    Chapter  Google Scholar 

  30. Roots R, Kraft G, Gosschalk E (1985) The formation of radiation-induced DNA breaks: the ratio of double-strand breaks to single-strand breaks. Int J Radiat Oncol Biol Phys 11(2):259–265

    Article  CAS  PubMed  Google Scholar 

  31. Povirk LF (2006) Biochemical mechanisms of chromosomal translocations resulting from DNA double-strand breaks. Dna Repair (amst) 5(9–10): p:1199–1212

    Article  Google Scholar 

  32. Corry PM, Cole A (1968) Radiation-induced double-strand scission of the DNA of mammalian metaphase chromosomes. Radiat Res 36(3):528–543

    Article  CAS  PubMed  Google Scholar 

  33. Lehmann AR, Ormerod MG (1970) Double-strand breaks in the DNA of a mammalian cell after x‑irradiation. Biochim Biophys Acta 217(2):268–277

    Article  CAS  PubMed  Google Scholar 

  34. Blöcher D (1982) DNA double strand breaks in Ehrlich ascites tumour cells at low doses of x‑rays. I. Determination of induced breaks by centrifugation at reduced speed. Int J Radiat Biol Relat Stud Phys Chem Med 42(3):317–328

    Article  PubMed  Google Scholar 

  35. Hagen U, Ullrich M, Jung H (1969) Transcription on irradiated DNA. Int J Radiat Biol Relat Stud Phys Chem Med 16(6):597–601

    Article  CAS  PubMed  Google Scholar 

  36. Jacobs A, Bopp A, Hagen U (1972) In vitro repair of single-strand breaks in -irradiated DNA by polynucleotide ligase. Int J Radiat Biol Relat Stud Phys Chem Med 22(5):431–435

    Article  CAS  PubMed  Google Scholar 

  37. Ward JF (1990) The yield of DNA double-strand breaks produced intracellularly by ionizing radiation: a review. Int J Radiat Biol 57(6):1141–1150

    Article  CAS  PubMed  Google Scholar 

  38. Timofeev-Resovskij NV, Zimmer KG (1947) Das Trefferprinzip in der Biologie. Hirzel

    Google Scholar 

  39. Zimmer KG (1961) Studies on Quantitative Radiation Biology. Hafner Publishing Company

    Google Scholar 

  40. Blakely EA et al (1979) Inactivation of human kidney cells by high-energy monoenergetic heavy-ion beams. Radiat Res 80(1):122–160

    Article  CAS  PubMed  Google Scholar 

  41. Hanawalt PC et al (1979) DNA repair in bacteria and mammalian cells. Annu Rev Biochem 48: p:783–836

    Article  Google Scholar 

  42. Patrick MH, Haynes RH (1964) Dark Recovery Phenomena in Yeast. II. Conditions That Modify The Recovery Process. Radiat Res 23: p:564–579

    Article  Google Scholar 

  43. Haynes RH, Eckardt F, Kunz BA (1984) The DNA damage-repair hypothesis in radiation biology: comparison with classical hit theory. Br J Cancer Suppl 6: p:81–90

    Google Scholar 

  44. Ward JF (2000) Complexity of damage produced by ionizing radiation. Cold Spring Harb Symp Quant Biol 65: p:377–382

    Article  Google Scholar 

  45. Maréchal A, Zou L (2013) DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb Perspect Biol 5(9):a012716 https://doi.org/10.1101/cshperspect.a012716

  46. Savitsky K et al (1995) A single ataxia telangiectasia gene with a product similar to PI‑3 kinase. Science 268(5218):1749–1753

    Article  CAS  PubMed  Google Scholar 

  47. Pritchard J et al (1982) The effects of radiation therapy for Hodgkin’s disease in a child with ataxia telangiectasia: a clinical, biological and pathologic study. Cancer 50(5):877–886

    Article  CAS  PubMed  Google Scholar 

  48. O’Driscoll M et al (2004) An overview of three new disorders associated with genetic instability: LIG4 syndrome, RS-SCID and ATR-Seckel syndrome. Dna Repair (amst) 3(8–9): p:1227–1235

    Article  Google Scholar 

  49. Borgmann K et al (2016) DNA Repair. Recent Results Cancer Res 198: p:1–24

    Google Scholar 

  50. Guirouilh-Barbat J et al (2014) Is homologous recombination really an error-free process? Front Genet 5: p:175

    Google Scholar 

  51. Hicks WM, Kim M, Haber JE (2010) Increased mutagenesis and unique mutation signature associated with mitotic gene conversion. Science 329(5987):82–85

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Steiner S et al (1995) Homologous recombination as the main mechanism for DNA integration and cause of rearrangements in the filamentous ascomycete Ashbya gossypii. Nat Genet 140(3):973–987

    CAS  Google Scholar 

  53. Yamamoto A et al (1996) Cell cycle-dependent expression of the mouse Rad51 gene in proliferating cells. Mol Gen Genet 251(1):1–12

    CAS  PubMed  Google Scholar 

  54. Makharashvili N, Paull Ct TTI (2015) A DNA damage response protein at the intersection of DNA metabolism. Dna Repair (amst) 32: p:75–81

    Article  Google Scholar 

  55. Cruz-García A, López-Saavedra A, Huertas P (2014) BRCA1 accelerates CtIP-mediated DNA-end resection. Cell Rep 9(2):451–459

    Article  PubMed  Google Scholar 

  56. Escribano-Diaz C, Durocher D (2013) DNA repair pathway choice—a PTIP of the hat to 53BP1. Embo Rep 14(8):665–666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Her J, Bunting SF (2018) How cells ensure correct repair of DNA double-strand breaks. J Biol Chem 293(27):10502–10511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sartori AA et al (2007) Human CtIP promotes DNA end resection. Nature 450(7169):509–514

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. van der Heijden MS et al (2004) Functional defects in the fanconi anemia pathway in pancreatic cancer cells. Am J Pathol 165(2):651–657

    Article  PubMed  PubMed Central  Google Scholar 

  60. Rosenberg PS, Tamary H, Alter BP (2011) How high are carrier frequencies of rare recessive syndromes? Contemporary estimates for Fanconi Anemia in the United States and Israel. Am J Med Genet A 155a(8):1877–1883

    Article  PubMed  Google Scholar 

  61. Cerbinskaite A et al (2012) Defective homologous recombination in human cancers. Cancer Treat Rev 38(2):89–100

    Article  CAS  PubMed  Google Scholar 

  62. Bryant HE et al (2009) PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination. Embo J 28(17):2601–2615

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Pearl LH et al (2015) Therapeutic opportunities within the DNA damage response. Nat Rev Cancer 15(3):166–180

    Article  CAS  PubMed  Google Scholar 

  64. Veatch W, Okada S (1969) Radiation-induced breaks of DNA in cultured mammalian cells. Biophys J 9(3):330–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Bradley MO, Kohn KW (1979) X‑ray induced DNA double strand break production and repair in mammalian cells as measured by neutral filter elution. Nucleic Acids Res 7(3):793–804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Iliakis GE, Cicilioni O, Metzger L (1991) Measurement of DNA double-strand breaks in CHO cells at various stages of the cell cycle using pulsed field gel electrophoresis: calibration by means of 125I decay. Int J Radiat Biol 59(2):343–357

    Article  CAS  PubMed  Google Scholar 

  67. Stamato TD, Denko N (1990) Asymmetric field inversion gel electrophoresis: a new method for detecting DNA double-strand breaks in mammalian cells. Radiat Res 121(2):196–205

    Article  CAS  PubMed  Google Scholar 

  68. Rogakou EP et al (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273(10):5858–5868

    Article  CAS  PubMed  Google Scholar 

  69. Wang X et al (2015) Unbiased detection of off-target cleavage by CRISPR-Cas9 and TALENs using integrase-defective lentiviral vectors. Nat Biotechnol 33(2):175–178

    Article  CAS  PubMed  Google Scholar 

  70. Menegakis A et al (2015) γH2AX assay in ex vivo irradiated tumour specimens: A novel method to determine tumour radiation sensitivity in patient-derived material. Radiother Oncol 116(3):473–479

    Article  PubMed  Google Scholar 

  71. Kordon MM et al (2020) STRIDE‑a fluorescence method for direct, specific in situ detection of individual single- or double-strand DNA breaks in fixed cells. Nucleic Acids Res 48(e14):3

    Google Scholar 

  72. Mateo J et al (2019) A decade of clinical development of PARP inhibitors in perspective. Ann Oncol 30(9):1437–1447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Turk AA, Wisinski KB (2018) PARP inhibitors in breast cancer: Bringing synthetic lethality to the bedside. Cancer 124(12):2498–2506

    Article  CAS  PubMed  Google Scholar 

  74. Cortesi L, Rugo HS, Jackisch C (2021) An Overview of PARP Inhibitors for the Treatment of Breast Cancer. Target Oncol 16(3):255–282

    Article  PubMed  PubMed Central  Google Scholar 

  75. Robson M et al (2017) Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 377(6):523–533

    Article  CAS  PubMed  Google Scholar 

  76. Robson ME et al (2019) OlympiAD final overall survival and tolerability results: Olaparib versus chemotherapy treatment of physician’s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer. Ann Oncol 30(4):558–566

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Litton JK et al (2020) Talazoparib versus chemotherapy in patients with germline BRCA1/2-mutated HER2-negative advanced breast cancer: final overall survival results from the EMBRACA trial. Ann Oncol 31(11):1526–1535

    Article  CAS  PubMed  Google Scholar 

  78. Geyer CE Jr. et al (2022) Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann Oncol 33(12):1250–1268

    Article  CAS  PubMed  Google Scholar 

  79. Foo T, George A, Banerjee S (2021) PARP inhibitors in ovarian cancer: An overview of the practice-changing trials. Genes Chromosomes Cancer 60(5):385–397

    Article  CAS  PubMed  Google Scholar 

  80. Banerjee S et al (2021) Maintenance olaparib for patients with newly diagnosed advanced ovarian cancer and a BRCA mutation (SOLO1/GOG 3004): 5‑year follow-up of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 22(12):1721–1731

    Article  CAS  PubMed  Google Scholar 

  81. González-Martín A et al (2019) Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 381(25):2391–2402

    Article  PubMed  Google Scholar 

  82. Moore K et al (2018) Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med 379(26):2495–2505

    Article  CAS  PubMed  Google Scholar 

  83. Tuli R et al (2019) A phase 1 study of veliparib, a PARP-1/2 inhibitor, with gemcitabine and radiotherapy in locally advanced pancreatic cancer. EBioMedicine 40: p:375–381

    Article  Google Scholar 

  84. Ray-Coquard I et al (2019) Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med 381(25):2416–2428

    Article  CAS  PubMed  Google Scholar 

  85. Derby SJ, Chalmers AJ, Carruthers RD (2022) Radiotherapy-Poly(ADP-ribose) Polymerase Inhibitor Combinations: Progress to Date. Semin Radiat Oncol 32(1):15–28

    Article  PubMed  Google Scholar 

  86. Verhagen CV et al (2015) 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 116(3):358–365

    Article  CAS  PubMed  Google Scholar 

  87. Colicchia V et al (2017) PARP inhibitors enhance replication stress and cause mitotic catastrophe in MYCN-dependent neuroblastoma. Oncogene 36(33):4682–4691

    Article  CAS  PubMed  Google Scholar 

  88. Zhan L et al (2016) Novel poly (ADP-ribose) polymerase inhibitor, AZD2281, enhances radiosensitivity of both normoxic and hypoxic esophageal squamous cancer cells. Dis Esophagus 29(3):215–223

    Article  CAS  PubMed  Google Scholar 

  89. LaFargue CJ et al (2019) Exploring and comparing adverse events between PARP inhibitors. Lancet Oncol 20(1):e15–e28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Karam SD et al (2018) Final Report of a Phase I Trial of Olaparib with Cetuximab and Radiation for Heavy Smoker Patients with Locally Advanced Head and Neck Cancer. Clin Cancer Res 24(20):4949–4959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. de Haan R et al (2021) Phase I and Pharmacologic Study of Olaparib in Combination with High-dose Radiotherapy with and without Concurrent Cisplatin for Non-Small Cell Lung Cancer. Clin Cancer Res 27(5):1256–1266

    Article  PubMed  Google Scholar 

  92. Chabot P et al (2017) Veliparib in combination with whole-brain radiation therapy for patients with brain metastases from non-small cell lung cancer: results of a randomized, global, placebo-controlled study. J Neurooncol 131(1):105–115

    Article  CAS  PubMed  Google Scholar 

  93. Gutierrez-Quintana R et al (2022) Radiation-induced neuroinflammation: a potential protective role for poly(ADP-ribose) polymerase inhibitors? Neurooncol Adv 4(vdab190):1

    Google Scholar 

  94. Lodovichi S et al (2020) Inhibition of DNA Repair in Cancer Therapy: Toward a Multi-Target Approach. Int J Mol Sci 21(18):6684. https://doi.org/10.3390/ijms21186684

  95. Monge-Cadet J et al (2022) DNA repair inhibitors and radiotherapy. Cancer Radiother 26(6–7):947–954

    Article  CAS  PubMed  Google Scholar 

  96. Huang AC, Zappasodi R (2022) A decade of checkpoint blockade immunotherapy in melanoma: understanding the molecular basis for immune sensitivity and resistance. Nat Immunol 23(5):660–670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Stone HB, Peters LJ, Milas L (1979) Effect of host immune capability on radiocurability and subsequent transplantability of a murine fibrosarcoma. J Natl Cancer Inst 63(5):1229–1235

    CAS  PubMed  Google Scholar 

  98. Lee Y et al (2009) Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment. Blood 114(3):589–595

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Demaria S, Formenti SC (2007) Sensors of ionizing radiation effects on the immunological microenvironment of cancer. Int J Radiat Biol 83(11–12):819–825

    Article  CAS  PubMed  Google Scholar 

  100. Larsson M, Fonteneau JF, Bhardwaj N (2001) Dendritic cells resurrect antigens from dead cells. Trends Immunol 22(3):141–148

    Article  CAS  PubMed  Google Scholar 

  101. Rückert M et al (2018) Immune modulatory effects of radiotherapy as basis for well-reasoned radioimmunotherapies. Strahlenther Onkol 194(6):509–519

    Article  PubMed  Google Scholar 

  102. Formenti SC, Demaria S (2009) Systemic effects of local radiotherapy. Lancet Oncol 10(7):718–726

    Article  PubMed  PubMed Central  Google Scholar 

  103. Prise KM et al (2005) New insights on cell death from radiation exposure. Lancet Oncol 6(7):520–528

    Article  CAS  PubMed  Google Scholar 

  104. Yin L et al (2020) Humanized mouse model: a review on preclinical applications for cancer immunotherapy. Am J Cancer Res 10(12):4568–4584

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674

    Article  CAS  PubMed  Google Scholar 

  106. Brix N et al (2017) Abscopal, immunological effects of radiotherapy: Narrowing the gap between clinical and preclinical experiences. Immunol Rev 280(1):249–279

    Article  CAS  PubMed  Google Scholar 

  107. Lauber K et al (2012) Dying cell clearance and its impact on the outcome of tumor radiotherapy. Front Oncol 2:116

    Article  PubMed  PubMed Central  Google Scholar 

  108. Long ZJ et al (2022) cGAS/STING cross-talks with cell cycle and potentiates cancer immunotherapy. Mol Ther 30(3):1006–1017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Kastan MB, Bartek J (2004) Cell-cycle checkpoints and cancer. Nature 432(7015):316–323

    Article  CAS  PubMed  Google Scholar 

  110. Mackenzie KJ et al (2017) cGAS surveillance of micronuclei links genome instability to innate immunity. Nature 548(7668):461–465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Vanpouille-Box C et al (2017) DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun 8:15618

    Article  PubMed  PubMed Central  Google Scholar 

  112. Rodríguez-Ruiz ME et al (2018) Immunological Mechanisms Responsible for Radiation-Induced Abscopal Effect. Trends Immunol 39(8):644–655

    Article  PubMed  PubMed Central  Google Scholar 

  113. Cercek A et al (2022) PD‑1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med 386(25):2363–2376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Rittberg R et al (2021) Immune Checkpoint Inhibition as Primary Adjuvant Therapy for an IDH1-Mutant Anaplastic Astrocytoma in a Patient with CMMRD: A Case Report-Usage of Immune Checkpoint Inhibition in CMMRD. Curr Oncol 28(1):757–766

    Article  PubMed  PubMed Central  Google Scholar 

  115. Concannon K et al (2023) Combining targeted DNA repair inhibition and immune-oncology approaches for enhanced tumor control. Mol Cell 83(5):660–680. https://doi.org/10.1016/j.molcel.2022.12.031

Download references

Acknowledgements

We gratefully acknowledge intense and fruitful discussions with Prof. Christian Streffer, Medical School, University Hospital Essen. The pictures in Fig. 1 were kindly provided by the Museum of the University of Tübingen (MUT).

Author information

Authors and Affiliations

  1. Translational Radiation Biology, Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany

    Benjamin Frey & Tina Jost

  2. Laboratory of Radiobiology and Radiation Oncology, Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Kerstin Borgmann

  3. Department of Radiation Oncology, University Hospital Muenster, Muenster, Germany

    Burkhard Greve & Michael Oertel

  4. Department of Radiotherapy and Radiation Oncology, Franziskus Hospital Bielefeld, Kiskerst. 26, 33615, Bielefeld, Germany

    Oliver Micke

  5. Department of Radiation Oncology, AKH, Comprehensive Cancer Center Vienna, Medical University Vienna, Vienna, Austria

    Franziska Eckert

Authors
  1. Benjamin Frey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kerstin Borgmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tina Jost
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Burkhard Greve
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Oertel
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Oliver Micke
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Franziska Eckert
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Oliver Micke.

Ethics declarations

Conflict of interest

F. Eckert has received speaker’s honoraria and travel grants from Dr. Sennewald GmbH. B. Frey, K. Borgmann, T. Jost, B. Greve, M. Oertel, and O. Micke declare that they have no competing interests.

Ethical standards

For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case.

Additional information

The authors Benjamin Frey and Kerstin Borgmann contributed equally to the manuscript.

This work was conceptualized and partly written by the history working group of the German Radiation Oncology Society (DEGRO).

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Frey, B., Borgmann, K., Jost, T. et al. DNA as the main target in radiotherapy—a historical overview from first isolation to anti-tumour immune response. Strahlenther Onkol 199, 1080–1090 (2023). https://doi.org/10.1007/s00066-023-02122-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00066-023-02122-5

Keywords

Search

Navigation