Overcoming of radiation resistances

C. Friesen; I. Hormann; M. Roscher; S. Bacher; E. Miltner

doi:10.1055/s-0038-1626536

Nuklearmedizin - NuclearMedicine, Table of Contents

Nuklearmedizin 2010; 49(S 01): S31-S36
DOI: 10.1055/s-0038-1626536

Übersichtsarbeit

Schattauer GmbH

Strahlenresistenzen und ihre Überwindung

Overcoming of radiation resistances

C. Friesen

¹Institut für Rechtsmedizin, Universität Ulm

,

I. Hormann^*

¹Institut für Rechtsmedizin, Universität Ulm

,

M. Roscher^*

¹Institut für Rechtsmedizin, Universität Ulm

,

S. Bacher^*

¹Institut für Rechtsmedizin, Universität Ulm

,

E. Miltner

¹Institut für Rechtsmedizin, Universität Ulm

› Author Affiliations

Abstract

Summary

Despite good achievements in prevention and control, cancer is still a leading cause of death worldwide. The development of resistances against conventional treatment modalities is one of the main causes of failure in the treatment of cancer. Radio- and chemotherapies fail frequently due to intrinsic or acquired resistances in apoptotic signalling pathways or alterations in DNA-repair processes.

Targeted radiotherapies employing α-particle-emitting radionuclides and Auger-emitting electrons are a promising approach in cancer treatment to break radio- and chemo – resistance by overcoming DNA-repair mechanisms and reversing deficient activation of apoptotic pathways in cancer cells.

Zusammenfassung

Trotz großer Fortschritte in der Krebstherapie zählen Tumorerkrankungen zu den häufigsten Todesursachen. Das Hauptproblem sind inhärente oder erworbene Resistenzen der Tumorzellen gegenüber konventionellen Therapien. Häufig spielen Defekte im Apoptosesignalweg sowie fehlregulierte DNA-Reparaturmechanismen eine entscheidende Rolle bei Strahlen- und Chemoresistenzen.

Die gezielte Radionuklidtherapie mit a- und Auger-Elektronen-Emittern ist ein vielversprechender Therapieansatz, um Resistenzen gegenüber Strahlung und Chemotherapeutika in Tumorzellen erfolgreich zu überwinden, indem die DNA-Reparatur durchbrochen wird und somit die apoptotischen Signalwege reaktiviert werden können.

Keywords

Cancer treatment - resistances - apoptosis - DNA-repair - α-emitter - Auger electrons

Schlüsselwörter

Krebsbehandlung - Resistenzen - Apoptose - DNA-Reparatur - α-Emitter - Auger-Elektronen

Full Text

References

Literatur
1 Bloomer WD, McLaughlin WH, Weichselbaum RR. et al. Iodine-125-labelled tamoxifen is differentially cytoxic to cells containing oestrogen receptors. Int J Radiat Biol Relat Stud Phys Chem Med 1980; 38: 197-202.
2 Brechbiel MW. Targeted alpha-therapy: past, present, future?. Dalton Trans 2007; 4918-4928.
3 Buchegger F, Perillo-Adamer F, Dupertuis YM, De laloye AB. Auger radiation targeted into DNA: a therapy perspective. Eur J Nucl Med Mol Imaging 2006; 33: 1352-1363.
4 Burz C, Berindan-Neagoe I, Balacescu O, Irimie A. Apoptosis in cancer: key molecular signaling pathways and therapy targets. Acta Oncol 2009; 48: 811-821.
5 Christmann M, Tomicic MT, Roos WP, Kaina B. Mechanisms of human DNA repair: an update. Toxicology 2003; 193: 3-34.
6 Cordier D, Forrer F, Bruchertseifer F. et al. Targeted alpha-radionuclide therapy of functionally critically located gliomas with ²¹³Bi-DOTA-[Thi8, Met(O2)11]-substance P: a pilot trial. Eur J Nucl Med Mol Imaging 2010; 37: 1335-1344.
7 Couturier O, Supiot S, Degraef-Mougin M. et al. Cancer radioimmunotherapy with alpha-eitting nuclides. Eur J Nucl Med Mol Imaging 2005; 32: 601-614.
8 Edwards BK, Ward E, Kohler BA, et al. Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer 2010; 116: 544-573.
9 Eriksson D, Stigbrand T. Radiation-induced cell death mechanisms. Tumour Biol 2010; 31: 363-372.
10 Eyler CE, Rich JN. Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol 2008; 26: 2839-2845.
11 Friesen C, Fulda S, Debatin KM. Deficient activation of the CD95 (APO-1/Fas) system in drug-resistant cells. Leukemia 1997; 11: 1833-1841.
12 Friesen C, Glatting G, Koop B, et al. Breaking chemoresistance and radioresistance with [²¹³Bi]anti-CD45 antibodies in leukemia cells. Cancer Res 2007; 67: 1950-1958.
13 Friesen C, Hormann I, Roscher M, et al. [²¹³Bi]Substance P is a promising approch to break chemo- and radioresistance in glioblastoma and glioblastoma stem cells. Nuklearmedizin 2010; 49: A37.
14 Friesen C, Lubatschofski A, Kotzerke J. et al. Beta-irradiation used for systemic radioimmunotherapy induces apoptosis and activates apoptosis pathways in leukaemia cells. Eur J Nucl Med Mol Imaging 2003; 30: 1251-1261.
15 Friesen C, Roscher M, Hormann I. et al. Targeted alpha therapy kills chemo- and radioresistant non- Hodgkin's lymphoma cells by activation of apoptosis pathways. Nuklearmedizin 2010; 49: A71.
16 Friesen C, Roscher M, Morgenstern A. et al. Differences in induction of cell death and activation of apoptosis pathways in myeloid leukemia cells using an anti-CD33 antibody radiolabeled with thorium-226 and bismuth-213. Nuklearmedizin 2009; 48: A6.
17 Friesen C, Roscher M, Morgenstern A. et al. Efficient killing of leukemia cells using an anti-CD33 antibody radiolabeled with thorium-226 or bismuth-213 depends strongly on specific activity. Nuklearmedizin 2009; 48: A7.
18 Friesen C, Uhl M, Pannicke U. et al. DNA-ligase IV and DNA-protein kinase play a critical role in deficient caspases activation in apoptosis-resistant cancer cells by using doxorubicin. Mol Biol Cell 2008; 19: 3283-3289.
19 Fulda S. Therapeutic opportunities for counteracting apoptosis resistance in childhood leukaemia. Br J Haematol 2009; 145: 441-454.
20 Fulda S, Galluzzi L, Kroemer G. Targeting mitochondria for cancer therapy. Nat Rev Drug Discov 2010; 9: 447-464.
21 Gerber DE, Chan TA. Recent advances in radiation therapy. Am Fam Physician 2008; 78: 1254-1262.
22 Guensberg P, Wacheck V, Lucas T. et al. Bcl-xL antisense oligonucleotides chemosensitize human glioblastoma cells. Chemotherapy 2002; 48: 189-195.
23 Kassis AI. Cancer therapy with Auger electrons: are we almost there?. J Nucl Med 2003; 44: 1479-1481.
24 Kassis AI. Therapeutic radionuclides: biophysical and radiobiologic principles. Semin Nucl Med 2008; 38: 358-366.
25 Kassis AI, Adelstein SJ. Radiobiologic principles in radionuclide therapy. J Nucl Med 2005; 46 Suppl 1 4S-12S.
26 Kassis AI, Fayad F, Kinsey BM. et al. Radiotoxicity of an 125I-labeled DNA intercalator in mammalian cells. Radiat Res 1989; 118: 283-294.
27 Kotzerke J, Bunjes D, Scheinberg DA. Radioimmu-noconjugates in acute leukemia treatment: the future is radiant. Bone Marrow Transplant 2005; 36: 1021-1026.
28 Lieber MR. The mechanism of human nonhomologous DNA end joining. J Biol Chem 2008; 283: 1-5.
29 Lomonosova E, Chinnadurai G. BH3-only proteins in apoptosis and beyond: an overview. Oncogene 2008; 27 Suppl 1 S2-19.
30 Mackey JR, Baldwin SA, Young JD, Cass CE. Nucleoside transport and its significance for anticancer drug resistance. Drug Resist Updat 1998; 1: 310-324.
31 Mulford DA, Scheinberg DA, Jurcic JG. The promise of targeted {alpha}-particle therapy. J Nucl Med 2005; 46 Suppl 1 199S-204S.
32 Raju MR, Eisen Y, Carpenter S, Inkret WC. Radiobiology of alpha particles. III. Cell inactivation by alpha-particle traversals of the cell nucleus. Radiat Res 1991; 128: 204-209.
33 Reske SN, Deisenhofer S, Glatting G. et al. ¹²³I-ITdU-mediated nanoirradiation of DNA efficiently induces cell kill in HL60 leukemia cells and in doxorubicin-, beta-, or gamma-radiation-resistant cell lines. J Nucl Med 2007; 48: 1000-1007.
34 Rockmann H, Schadendorf D. Drug resistance in human melanoma: mechanisms and therapeutic opportunities. Onkologie 2003; 26: 581-587.
35 Runge R, Wendisch M, Wunderlich G. et al. DNASchäden von Lymphozyten nach Bestrahlung mit ²¹¹At und ¹⁸⁸Re – Quantifizierung mit dem alkalischen und neutralen Komet-Assay. Nuklearmedizin 2009; 48: 221-226.
36 Sastry KS. Biological effects of the Auger emitter iodine-125: a review. Report No. 1 of AAPM Nuclear Medicine Task Group No. 6. Med Phys 1992; 19: 1361-1370.
37 Schimmer AD, Dalili S, Batey RA, Riedl SJ. Targeting XIAP for the treatment of malignancy. Cell Death Differ 2006; 13: 179-188.
38 Schimmer AD, Munk-Pedersen I, Minden MD, Reed JC. Bcl-2 and apoptosis in chronic lymphocytic leukemia. Curr Treat Options Oncol 2003; 4: 211-218.
39 Stepanek J, Larsson B, Weinreich R. Auger-electron spectra of radionuclides for therapy and diagnostics. Acta Oncol 1996; 35: 863-868.
40 Welsh JS. Beta decay in science and medicine. Am J Clin Oncol 2007; 30: 437-439.
41 Zalutsky MR, Bigner DD. Radioimmunotherapy with alpha-particle emitting radioimmunoconjugates. Acta Oncol 1996; 35: 373-379.
42 Zalutsky MR, Reardon DA, Akabani G. et al. Clinical experience with alpha-particle emitting ²¹¹At: treatment of recurrent brain tumor patients with ²¹¹At-labeled chimeric antitenascin monoclonal antibody 81C6. J Nucl Med 2008; 49: 30-38.
43 Zalutsky MR, Reardon DA, Pozzi OR. et al. Targeted alpha-particle radiotherapy with ²¹¹At-labeled monoclonal antibodies. Nucl Med Biol 2007; 34: 779-785.