Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Häufige urologisch-sexualmedizinische Themen in der Praxis sind das Thema des MMW-Webinars am 5. Juni von 17.30 bis 19 Uhr. Konkret geht es um die Frage, wann bei Harnwegsinfektionen auf Antibiotika verzichtet werden kann, und um ein Update zur Therapie von Libido- und Potenzstörungen des Mannes. Der dritte Vortrag behandelt sexuell übertragbare Krankheiten. Stellen Sie Ihre Fragen an die Experten und sammeln Sie 2 CME-Punkte. Jetzt gleich anmelden!
Erweiterte Suche
Anmelden
nach oben
Strahlentherapie und Onkologie
Erschienen in: Strahlentherapie und Onkologie 12/2023

24.08.2023 | Review Article

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

verfasst von: Benjamin Frey, Kerstin Borgmann, Tina Jost, Burkhard Greve, Michael Oertel, Dr. Oliver Micke, Franziska Eckert

Erschienen in: Strahlentherapie und Onkologie | Ausgabe 12/2023

Einloggen, um Zugang zu erhalten

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.
Literatur
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):231–244PubMedCrossRef
2.
3.
Kirsch DG et al (2018) The Future of Radiobiology. J Natl Cancer Inst 110(4):329–340PubMedCrossRef
4.
Mavragani IV et al (2016) Key mechanisms involved in ionizing radiation-induced systemic effects. A current review. Toxicol Res (camb) 5(1):12–33PubMedCrossRef
5.
Gaipl US et al (2014) Kill and spread the word: stimulation of antitumor immune responses in the context of radiotherapy. Immunotherapy 6(5):597–610PubMedCrossRef
6.
Abuodeh Y, Venkat P, Kim S (2016) Systematic review of case reports on the abscopal effect. Curr Probl Cancer 40(1):25–37PubMedCrossRef
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):451–484PubMedCrossRef
8.
Dahm R, Discovering DNA (2008) Friedrich Miescher and the early years of nucleic acid research. Hum Genet 122(6):565–581PubMedCrossRef
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):1–84PubMedCrossRef
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):75–79PubMedPubMedCentralCrossRef
11.
12.
Muller HJ (1699) Artificial Transmutation of the Gene. Science p:84–87
13.
14.
15.
Watson JD, Crick FH (1953) Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid. Nature 171(4356):737–738PubMedCrossRef
16.
Watson JD, Crick FH (1953) Genetical implications of the structure of deoxyribonucleic acid. Nature 171(4361):964–967PubMedCrossRef
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):351–353PubMedCrossRef
18.
Watson JD (2007) Die Doppelhelix, 20th ed edn. Rowohlt, Hamburg
19.
Schuster RC (1964) Dark Repair Of Ultraviolet Injury In E. Coli During Deprivation Of Thymine. Nature 202: p:614–615CrossRef
20.
Nobel Prizes for Medicine, 1968. Nature, 1968. 220(5165):324–325
21.
22.
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):37–41PubMed
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):253–284PubMedPubMedCentralCrossRef
25.
26.
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:309–326CrossRef
28.
Krylov V, Tlapakova T (2015) Xenopus Cytogenetics and Chromosomal Evolution. Cytogenet Genome Res 145(3–4):192–200PubMedCrossRef
29.
Streffer C (1980) Biologische Grundlagen der Strahlentherapie. In: Scherer E (ed) Strahlentherapie: Radiologische Onkologie. Springer Berlin Heidelberg, Berlin, Heidelberg, pp 197–266CrossRef
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):259–265PubMedCrossRef
31.
Povirk LF (2006) Biochemical mechanisms of chromosomal translocations resulting from DNA double-strand breaks. Dna Repair (amst) 5(9–10): p:1199–1212CrossRef
32.
Corry PM, Cole A (1968) Radiation-induced double-strand scission of the DNA of mammalian metaphase chromosomes. Radiat Res 36(3):528–543PubMedCrossRef
33.
Lehmann AR, Ormerod MG (1970) Double-strand breaks in the DNA of a mammalian cell after x‑irradiation. Biochim Biophys Acta 217(2):268–277PubMedCrossRef
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):317–328PubMedCrossRef
35.
Hagen U, Ullrich M, Jung H (1969) Transcription on irradiated DNA. Int J Radiat Biol Relat Stud Phys Chem Med 16(6):597–601PubMedCrossRef
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):431–435PubMedCrossRef
37.
Ward JF (1990) The yield of DNA double-strand breaks produced intracellularly by ionizing radiation: a review. Int J Radiat Biol 57(6):1141–1150PubMedCrossRef
38.
Timofeev-Resovskij NV, Zimmer KG (1947) Das Trefferprinzip in der Biologie. Hirzel
39.
Zimmer KG (1961) Studies on Quantitative Radiation Biology. Hafner Publishing Company
40.
Blakely EA et al (1979) Inactivation of human kidney cells by high-energy monoenergetic heavy-ion beams. Radiat Res 80(1):122–160PubMedCrossRef
41.
Hanawalt PC et al (1979) DNA repair in bacteria and mammalian cells. Annu Rev Biochem 48: p:783–836CrossRef
42.
Patrick MH, Haynes RH (1964) Dark Recovery Phenomena in Yeast. II. Conditions That Modify The Recovery Process. Radiat Res 23: p:564–579CrossRef
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
44.
Ward JF (2000) Complexity of damage produced by ionizing radiation. Cold Spring Harb Symp Quant Biol 65: p:377–382CrossRef
45.
46.
Savitsky K et al (1995) A single ataxia telangiectasia gene with a product similar to PI‑3 kinase. Science 268(5218):1749–1753PubMedCrossRef
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):877–886PubMedCrossRef
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:1227–1235CrossRef
49.
Borgmann K et al (2016) DNA Repair. Recent Results Cancer Res 198: p:1–24
50.
Guirouilh-Barbat J et al (2014) Is homologous recombination really an error-free process? Front Genet 5: p:175
51.
Hicks WM, Kim M, Haber JE (2010) Increased mutagenesis and unique mutation signature associated with mitotic gene conversion. Science 329(5987):82–85PubMedPubMedCentralCrossRef
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
53.
Yamamoto A et al (1996) Cell cycle-dependent expression of the mouse Rad51 gene in proliferating cells. Mol Gen Genet 251(1):1–12PubMed
54.
Makharashvili N, Paull Ct TTI (2015) A DNA damage response protein at the intersection of DNA metabolism. Dna Repair (amst) 32: p:75–81CrossRef
55.
Cruz-García A, López-Saavedra A, Huertas P (2014) BRCA1 accelerates CtIP-mediated DNA-end resection. Cell Rep 9(2):451–459PubMedCrossRef
56.
57.
58.
59.
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):1877–1883PubMedCrossRef
61.
Cerbinskaite A et al (2012) Defective homologous recombination in human cancers. Cancer Treat Rev 38(2):89–100PubMedCrossRef
62.
Bryant HE et al (2009) PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination. Embo J 28(17):2601–2615PubMedPubMedCentralCrossRef
63.
Pearl LH et al (2015) Therapeutic opportunities within the DNA damage response. Nat Rev Cancer 15(3):166–180PubMedCrossRef
64.
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):793–804PubMedPubMedCentralCrossRef
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):343–357PubMedCrossRef
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):196–205PubMedCrossRef
68.
Rogakou EP et al (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273(10):5858–5868PubMedCrossRef
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):175–178PubMedCrossRef
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):473–479PubMedCrossRef
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
72.
73.
Turk AA, Wisinski KB (2018) PARP inhibitors in breast cancer: Bringing synthetic lethality to the bedside. Cancer 124(12):2498–2506PubMedCrossRef
74.
75.
Robson M et al (2017) Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med 377(6):523–533PubMedCrossRef
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):558–566PubMedPubMedCentralCrossRef
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):1526–1535PubMedCrossRef
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):1250–1268PubMedCrossRef
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):385–397PubMedCrossRef
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):1721–1731PubMedCrossRef
81.
González-Martín A et al (2019) Niraparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med 381(25):2391–2402PubMedCrossRef
82.
Moore K et al (2018) Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med 379(26):2495–2505PubMedCrossRef
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:375–381CrossRef
84.
Ray-Coquard I et al (2019) Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med 381(25):2416–2428PubMedCrossRef
85.
Derby SJ, Chalmers AJ, Carruthers RD (2022) Radiotherapy-Poly(ADP-ribose) Polymerase Inhibitor Combinations: Progress to Date. Semin Radiat Oncol 32(1):15–28PubMedCrossRef
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):358–365PubMedCrossRef
87.
Colicchia V et al (2017) PARP inhibitors enhance replication stress and cause mitotic catastrophe in MYCN-dependent neuroblastoma. Oncogene 36(33):4682–4691PubMedCrossRef
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):215–223PubMedCrossRef
89.
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):4949–4959PubMedPubMedCentralCrossRef
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):1256–1266PubMedCrossRef
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):105–115PubMedCrossRef
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
94.
95.
Monge-Cadet J et al (2022) DNA repair inhibitors and radiotherapy. Cancer Radiother 26(6–7):947–954PubMedCrossRef
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):660–670PubMedPubMedCentralCrossRef
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):1229–1235PubMed
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):589–595PubMedPubMedCentralCrossRef
99.
Demaria S, Formenti SC (2007) Sensors of ionizing radiation effects on the immunological microenvironment of cancer. Int J Radiat Biol 83(11–12):819–825PubMedCrossRef
100.
Larsson M, Fonteneau JF, Bhardwaj N (2001) Dendritic cells resurrect antigens from dead cells. Trends Immunol 22(3):141–148PubMedCrossRef
101.
Rückert M et al (2018) Immune modulatory effects of radiotherapy as basis for well-reasoned radioimmunotherapies. Strahlenther Onkol 194(6):509–519PubMedCrossRef
102.
103.
Prise KM et al (2005) New insights on cell death from radiation exposure. Lancet Oncol 6(7):520–528PubMedCrossRef
104.
Yin L et al (2020) Humanized mouse model: a review on preclinical applications for cancer immunotherapy. Am J Cancer Res 10(12):4568–4584PubMedPubMedCentral
105.
Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674PubMedCrossRef
106.
Brix N et al (2017) Abscopal, immunological effects of radiotherapy: Narrowing the gap between clinical and preclinical experiences. Immunol Rev 280(1):249–279PubMedCrossRef
107.
108.
109.
Kastan MB, Bartek J (2004) Cell-cycle checkpoints and cancer. Nature 432(7015):316–323PubMedCrossRef
110.
111.
112.
113.
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):757–766PubMedPubMedCentralCrossRef
115.
Metadaten
Titel
DNA as the main target in radiotherapy—a historical overview from first isolation to anti-tumour immune response
verfasst von
Benjamin Frey
Kerstin Borgmann
Tina Jost
Burkhard Greve
Michael Oertel
Dr. Oliver Micke
Franziska Eckert
Publikationsdatum
24.08.2023
Verlag
Springer Berlin Heidelberg
Erschienen in
Strahlentherapie und Onkologie / Ausgabe 12/2023
Print ISSN: 0179-7158
Elektronische ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-023-02122-5

Weitere Artikel der Ausgabe 12/2023

Strahlentherapie und Onkologie 12/2023 Zur Ausgabe

Original Article

Effect of lethal total body irradiation on bone marrow chimerism, acute graft-versus-host disease, and tumor engraftment in mouse models: impact of different radiation techniques using low- and high-energy X-rays

Literatur kommentiert

Kombination stereotaktischer Radiotherapie mit Checkpointinhibitoren: Ergebnisse der CHEERS-Phase-II-Studie

Original Article

Normofractionated irradiation and not temozolomide modulates the immunogenic and oncogenic phenotype of human glioblastoma cell lines

Original Article

Tumor-specific radiosensitizing effect of the ATM inhibitor AZD0156 in melanoma cells with low toxicity to healthy fibroblasts

Literatur kommentiert

Organerhaltende Behandlung bei nodal-positiven Harnblasenkarzinomen

Review Article

Crosstalk between immune checkpoint and DNA damage response inhibitors for radiosensitization of tumors

Neu im Fachgebiet Onkologie

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

29.05.2024 Larynxkarzinom Nachrichten

Fast ein Viertel der Personen mit mäßig dysplastischen Stimmlippenläsionen entwickelt einen Kehlkopftumor. Solche Personen benötigen daher eine besonders enge ärztliche Überwachung.

15% bedauern gewählte Blasenkrebs-Therapie

29.05.2024 Urothelkarzinom Nachrichten

Ob Patienten und Patientinnen mit neu diagnostiziertem Blasenkrebs ein Jahr später Bedauern über die Therapieentscheidung empfinden, wird einer Studie aus England zufolge von der Radikalität und dem Erfolg des Eingriffs beeinflusst.

Erhöhtes Risiko fürs Herz unter Checkpointhemmer-Therapie

28.05.2024 Nebenwirkungen der Krebstherapie Nachrichten

Kardiotoxische Nebenwirkungen einer Therapie mit Immuncheckpointhemmern mögen selten sein – wenn sie aber auftreten, wird es für Patienten oft lebensgefährlich. Voruntersuchung und Monitoring sind daher obligat.

Costims – das nächste heiße Ding in der Krebstherapie?

28.05.2024 Onkologische Immuntherapie Nachrichten

„Kalte“ Tumoren werden heiß – CD28-kostimulatorische Antikörper sollen dies ermöglichen. Am besten könnten diese in Kombination mit BiTEs und Checkpointhemmern wirken. Erste klinische Studien laufen bereits.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise